U.S. patent application number 15/799081 was filed with the patent office on 2018-05-24 for biomedical sensing methods and apparatus for the detection and prevention of lung cancer states.
The applicant listed for this patent is Johnson & Johnson Vision Care, Inc.. Invention is credited to Frederick A. Flitsch, Randall B. Pugh, Adam Toner.
Application Number | 20180144092 15/799081 |
Document ID | / |
Family ID | 60661700 |
Filed Date | 2018-05-24 |
United States Patent
Application |
20180144092 |
Kind Code |
A1 |
Flitsch; Frederick A. ; et
al. |
May 24, 2018 |
BIOMEDICAL SENSING METHODS AND APPARATUS FOR THE DETECTION AND
PREVENTION OF LUNG CANCER STATES
Abstract
The present invention relates to methods and apparatus to
monitor and potentially prevent occurrences of lung cancer in
patients. The invention includes apparatus and methods to determine
a patient's pre-disposition or propensity to acquire lung cancer.
Also included are apparatus and methods to monitor for patient
biomarkers and for environmental agents, to warn and to take action
to reduce exposure to environmental agents and to increase patient
screening for the occurrence of lung cancer.
Inventors: |
Flitsch; Frederick A.; (New
Windsor, NY) ; Pugh; Randall B.; (Jacksonville,
FL) ; Toner; Adam; (Jacksonville, FL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Johnson & Johnson Vision Care, Inc. |
Jacksonville |
FL |
US |
|
|
Family ID: |
60661700 |
Appl. No.: |
15/799081 |
Filed: |
October 31, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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62424719 |
Nov 21, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 2560/0242 20130101;
C12Q 1/6886 20130101; Y02A 50/20 20180101; G16B 20/00 20190201;
A61B 5/68 20130101; G01N 2333/35 20130101; G01N 33/0049 20130101;
A61B 5/0816 20130101; A61B 5/02438 20130101; G01T 1/16 20130101;
A61B 2503/20 20130101; G01N 33/0047 20130101; G06F 19/3418
20130101; G16B 30/00 20190201; G16B 25/00 20190201; G01N 15/06
20130101; C12Q 2600/156 20130101; G01N 2015/0038 20130101; A61B
5/082 20130101; A61B 5/6861 20130101; A61B 5/6867 20130101; A61B
5/145 20130101; C12Q 1/04 20130101; G01N 33/0055 20130101; G16H
50/30 20180101; G01N 33/497 20130101 |
International
Class: |
G06F 19/22 20060101
G06F019/22; G01N 33/00 20060101 G01N033/00; G01N 33/497 20060101
G01N033/497; C12Q 1/04 20060101 C12Q001/04; C12Q 1/68 20060101
C12Q001/68; G06F 19/20 20060101 G06F019/20; G01T 1/16 20060101
G01T001/16; G01N 15/06 20060101 G01N015/06; A61B 5/00 20060101
A61B005/00; A61B 5/08 20060101 A61B005/08; A61B 5/024 20060101
A61B005/024 |
Claims
1. A system for detecting a form of cancer, the system comprising:
a means for obtaining genetic data of a patient to determine
variation at target locations of the patient's genome, wherein the
variations are related to an increased risk of having the form of
cancer; a first database record, wherein the first database record
contains records of familial health history; a second database
record, wherein the second database record contains one or more of
a null dataset and a record of an environmental exposure of the
patient; a first sensor system, wherein the first sensor system is
configured to sense biomarkers related to a cancer state, wherein
the biomarkers emanate from the user; a second sensor system,
wherein the second sensor system is configured to sense the local
environment of the user for one or more of particulate matter and
chemical pollutants; a processing system implementing at least one
of: a first algorithm which processes data from the first sensor
system to compare a first sensor system result to a threshold
level, wherein the threshold level is determined based on one or
more of: i) a result of the determined variation at target
locations of the patient's genome, ii) the first database record,
and iii) the second database record. and a second algorithm which
processes data from the second sensor to determine environmental
conditions at the patient's location; and a feedback device
configured to communicate a signal to the patient based on the
results of processing by the processing system.
2. The system of claim 1 wherein the first sensor system is a
non-specific chemical sensor.
3. The system of claim 1 wherein the second sensor system is a
non-specific chemical sensor.
4. The system of claim 3 wherein a plurality of elements in the
non-specific chemical sensor respond to an exposure to a chemical
in an environment surrounding the non-specific chemical sensor in a
pattern of responses which are correlated to a first chemical
suspected of being related to an increased risk for developing lung
cancer in the patient.
5. The system of claim 4 wherein the first chemical is radon.
6. The system of claim 4 wherein the first chemical is
bis(chloromethyl) ether.
7. The system of claim 4 wherein the first chemical is of a family
of polycyclic aromatic hydrocarbons.
8. The system of claim 3 wherein the non-specific chemical sensor
comprises a polymer film doped with chemical species that modulate
the absorbent properties of a surface of the polymer film.
9. The system of claim 3 wherein the non-specific chemical sensor
comprises crystals whose natural oscillation frequency is modulated
by absorbance of materials onto surfaces or onto films applied to
surfaces of the crystal.
10. The system of claim 1 wherein the first sensor system detects
biomarkers of lung cancer in the breath of the patient.
11. The system of claim 1 wherein the second sensor system is a
particulate sensing device.
12. The system of claim 1 wherein the second sensor system senses
at least a first biological agent.
13. The system of claim 12 wherein the biological agent is
Mycobacterium tuberculosis.
14. The system of claim 1 further comprising a stationary sensing
system that senses the work environment surrounding the patient
while they are at work.
15. The system of claim 14 wherein the stationary sensing system
senses radioactivity.
16. The system of claim 14 wherein the stationary sensing sensor
includes chemical exposure sensing.
17. The system of claim 14 wherein the stationary sensing system
includes particulate exposure sensing.
18. The system of claim 14 wherein the stationary sensing system
includes blood sensing.
19. The system of claim 14 wherein the stationary sensing system
includes sensing of a biometric.
20. The system of claim 19 wherein the biometric is inhalation
rate.
21. The system of claim 19 wherein the biometric is the patient's
pulse.
22. The system of claim 1 wherein the first sensor system that is
located within the patient's lung.
23. The system of claim 1 wherein the first sensor system that is
located within the patient's lung senses chemical markers.
24. The system of claim 1 wherein the first sensor system that is
located within the patient's lung senses exposure to environmental
chemicals.
25. The system of claim 1 wherein at least one of the first sensor
system and the second sensor system configures its wireless
communications devices into a mesh network topology with other
regionally distributed sensor systems.
26. A method of reducing a risk of acquiring lung cancer of a
patient predisposed to acquiring lung cancer, the method
comprising: determining the predisposition of the patient to
acquiring lung cancer by analyzing the patient's genome;
determining the predisposition of the patient to acquiring lung
cancer by analyzing the patient's family history; determining the
predisposition of the patient to acquiring lung cancer by analyzing
the patient's environment exposure history; activating a first
sensor system, wherein the first sensor system is configured to
sense biomarkers related to a cancer state, and wherein the
biomarkers emanate from the user; activating a second sensor
system, wherein the second sensor system is configured to sense the
local environment of the user for one or more of particulate matter
and chemical pollutants; activating a processing system, wherein
the processing system performs a first algorithm which processes
stored data originating from the first sensor system and
originating from the second sensor system and determines a status
to a threshold level, wherein the threshold level is determined at
least in part based on the analysis of the patient's genome;
activating a feedback device, wherein the feedback device
communicates a signal to the patient based on the status to the
alarm level; monitoring a first environmental status surrounding
the patient with the second sensing system; monitoring a biomarker
emanating from the patient with the second sensing device;
detecting a result from one or more of the first sensor system or
the second sensor system, wherein the result exceeds the threshold
level; communicating a signal to the patient based on the detected
result; and taking an action to reduce the exposure of the patient
to one or more of the first environmental status or the second
environmental status.
27. The method according to claim 26 wherein the second sensor
system is a non-specific chemical sensor.
28. The method according to claim 27 wherein a plurality of
elements in the non-specific chemical sensor respond to an exposure
to a chemical in an environment surrounding the non-specific
chemical sensor in a pattern of responses which are correlated to a
first chemical suspected of being related to an increased risk for
developing lung cancer in the patient.
29. The method according to claim 28 wherein the first chemical is
asbestos.
30. The method according to claim 28 wherein the first chemical is
bis(chloromethyl) ether.
31. The method according to claim 28 wherein the first chemical is
of a family of polycyclic aromatic hydrocarbons.
32. The method according to claim 27 wherein the non-specific
chemical sensor comprises a polymer film doped with chemical
species that modulates the absorbent properties of a surface of the
polymer film.
33. The method according to claim 27 wherein the non-specific
chemical sensor comprises crystals whose natural oscillation
frequency is modulated by absorbance of materials onto surfaces or
onto films applied to surfaces of the crystal.
34. The method according to claim 26 wherein the second sensor
system comprises a particulate sensing device.
35. The method according to claim 26 wherein the second sensor
system senses at least a first biological agent.
36. The method according to claim 35 wherein the biological agent
is Mycobacterium tuberculosis.
37. The method according to claim 26 further comprising installing
a stationary sensor system that senses the environment of the
workplace of the patient.
38. The method according to claim 37 wherein the stationary sensor
system senses radioactivity.
39. The method according to claim 37 wherein the stationary sensor
system includes chemical exposure sensing.
40. The method according to claim 37 wherein the stationary sensor
system includes particulate exposure sensing.
41. The method according to claim 37 wherein the stationary sensor
system includes blood sensing.
42. The method according to claim 37 wherein the stationary sensor
system includes sensing of a biometric.
43. The method according to claim 42 wherein the biometric is
inhalation rate.
44. The method according to claim 42 wherein the biometric is the
patient's pulse.
45. A system for reducing a potential risk of obtaining cancer, the
system comprising: a means for obtaining genetic data of a patient
to determine variation at target locations of the patient's genome,
wherein the variations are related to an increased risk of having
the form of cancer; a first sensing device wherein the first
sensing device is installed in a location of the home of the
patient; a second sensing device wherein the second sensing device
is installed in a location of the work location of the patient; a
processing system, wherein the processing system performs a first
algorithm which processes stored data originating from the first
sensing device and originating from the second sensing device and
determines a status to a threshold level, wherein the threshold
level is determined based on a result of the determined variation
at target regions of the patient's genome; and a feedback device,
wherein the feedback device communicates a signal to the patient
based on the status to the alarm level.
46. A system for detecting a form of cancer, the system comprising:
a means for obtaining genetic data of a patient to determine
variation at target locations of the patient's genome, wherein the
variations are related to an increased risk of having the form of
cancer; a first database record, wherein the first database record
contains records of familial health history; a second database
record, wherein the second database record contains one or more of
a null dataset and a record of an environmental exposure of the
patient; a first sensor system, wherein the first sensor system is
configured to sense biomarkers related to a cancer state, wherein
the biomarkers emanate from the user; a second sensor system,
wherein the second sensor system is configured to sense the local
environment of the user for one or more of particulate matter and
chemical pollutants; a processing system implementing at least one
of: a first algorithm which processes data from the first sensor
system to compare a first sensor system result to a threshold
level, wherein the threshold level is determined based on one or
more of: i) a result of the determined variation at target
locations of the patient's genome, ii) the first database record,
and iii) the second database record; and a second algorithm which
processes data from the second sensor to determine environmental
conditions at the patient's location; wherein the first sensor
system comprises a local neural network processing device; and a
feedback device configured to communicate a signal to the patient
based on the results of processing by the processing system.
Description
CROSS-REFRENCE TO RELATED APPLICATIONS
[0001] This patent application claims the benefit of U.S.
Provisional Patent Application No. 62/424,719 filed Nov. 21, 2016.
The contents are hereby incorporated by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
[0002] The present invention relates to methods and apparatus to
monitor and potentially prevent occurrences of lung cancer in
patients. The field includes apparatus and methods to determine a
patient's pre-disposition or propensity to acquire lung cancer.
2. Discussion of the Related Art
[0003] Cancer is not a single disease, but rather a collection of
related diseases that can start essentially anywhere in the body.
Common amongst all types of cancer is that the body's cells begin
to divide without stopping, proliferating and potentially spreading
into surrounding tissues. In the normal course of events, cells
grow and divide to form new cells as required by the body and when
they become damaged or old, they die and new cells replace the
damaged or old cells; however, cancer interrupts this process. With
cancer, the cells become abnormal, and cells that should die do not
and new cells form when they are not needed. These new cells can
reproduce or proliferate without stopping and may form growths
called tumors.
[0004] Cancerous tumors are malignant, which means they can spread
into or invade surrounding health tissue. In addition, cancer cells
can break off and travel to remote areas in the body through blood
or in the lymph system. Benign tumors, unlike malignant tumors, do
not spread or invade surrounding tissue; however, they may grow
large and cause damage. Both malignant and benign tumors may be
removed or treated. Malignant tumors tend to grow back whereas
benign tumors can grow back, but are much less likely to do so.
[0005] Cancer is a genetic disease in that it is caused by changes
in the genes that control the ways cells function, especially in
how they grow and divide. Genetic changes that cause cancer may be
inherited or they may arise over an individual's lifetime as a
result of errors that occur as cells divide or because of damage to
DNA caused by certain environmental exposure, for example,
industrial/commercial chemicals and ultraviolet light. The genetic
changes that may cause cancer tend to affect three types of genes;
namely proto-oncogenes which are involved in normal cell growth and
division, tumor suppressor genes which are also involved in
controlling cell growth and division, and DNA repair genes which,
as the name implies, are involved in repairing damaged DNA.
[0006] More than one-hundred distinct types of cancer have been
identified. The type of cancer may be named for the organ or tissue
where the cancers arise, for example, lung cancer, or the type of
cell that formed them, for example squamous cell cancer. Cancer,
unfortunately, is a leading cause of death both in the United
States and world-wide. According to the World Health Organization,
the number of new cancer cases will rise to twenty-five (25)
million per year over the next two decades.
[0007] Lung cancer is one of the most common cancers today.
According to the World Cancer Report 2014 from the World Health
Organization, lung cancer occurred in 14 million people and
resulted in 8.8 million deaths world-wide, making it the most
common cause of cancer-related death in men and the second most
common cause of cancer-related death in women. Lung cancer or lung
carcinoma is a malignant lung tumor that if left untreated can
metastasize into neighboring tissues and organs. The majority of
lung cancer is caused by long-term tobacco smoking; however, about
10 to 15 percent of lung cancer cases are not tobacco related.
These non-tobacco cases are most often caused by a combination of
genetic factors and exposure to certain environmental conditions,
including radon gas, asbestos, second-hand tobacco smoke, other
forms of air pollution, and other agents. The chance of surviving
lung cancer as well as other forms of lung cancer depends on early
detection and treatment.
[0008] As set forth above, cancer may be caused by a combination of
genetic factors and environmental factors. Accordingly, individuals
with a genetic predisposition towards cancer, for example lung
cancer, should preferably be monitored for exposure to
environmental factors that are known to cause or trigger this
genetic cascade. Sensors or sensor arrays may be adapted to detect
analytes in the environment and alert individuals of the potential
risk of exposure as well as to detect analytes produced by cancer
cells for early detection. The sensor array would preferably be
portable and configured to sample both analytes in the environment
and produced by individuals, for example, analyze breath and/or
other bodily emissions. It would be desired to develop protocols
that could be based on patient pre-disposition to lung cancer and
would associate appropriate levels of environmental monitoring and
patient screening contingent upon the genetically determined
pre-disposition to lung cancer.
SUMMARY OF THE INVENTION
[0009] Accordingly, methods and apparatus to monitor the
environment of genetically pre-dispositioned patients and warn them
to take action are disclosed herein. Additionally, methods and
apparatus to sense the emissions, biofluids, biome and biometrics
of the pre-dispositioned patients are also disclosed. Patients who
receive a warning may take action including additional periodic
screenings, avoiding locations with the potential for undesired
exposure to levels of environmental agents which may be correlated
with increased lung cancer risk for pre-disposed patients. In some
examples, the action that the patient takes may include the donning
of protective apparel such as masks with adsorbent material or
filters. The apparatus may sense the level of exposure of the
patient and record the results in a database. In some examples, the
Patient may wear the monitoring apparatus to a doctor visit with
the data logged on the device. The historical record of exposure
may be used by medical professionals to determine the level of
screening to be performed on the patient such as in a non-limiting
example computed tomography (CT) x-ray scanning of the lungs of the
patient.
[0010] In an example, a system for reducing a potential risk of
obtaining cancer may be formed comprising a number of pieces of
apparatus. In some examples, the system may include a thermal
cycler for performing genetic amplification, wherein the result of
the genetic amplification is used in determining a sequence of DNA
of a patient to determine variation at target regions of a
patient's genome. The system may include a first sensing device
wherein the first sensing device is installed in a location of the
home of the patient. The system may include a second sensing device
wherein the second sensing device is installed in a location of the
work location of the patient. The system may include a processing
system, wherein the processing system performs a first algorithm
which processes stored data originating from the first sensing
device and originating from the second sensing device and
determines a status to a threshold level, wherein the threshold
level is determined based on a result of the determined variation
at target regions of the patient's genome. In some examples, a
third sensing device may be associated with the patient themselves,
such as a sensing apparatus attached to or incorporated into a
smartphone or other wearable device. The system may also include a
feedback device, wherein the feedback device communicates a signal
to the patient based on the status to the alarm level. In
alternative embodiments, the system may be implemented as a
stand-alone or self-contained device, such as a device that may be
worn or carried.
[0011] This composition of the system may have various flexibility
in the nature of the components. In an example, the system may
include examples where the first sensing device is a non-specific
chemical sensor. In an example, the system may include examples
where a plurality of elements in the non-specific chemical sensor
respond to an exposure to a chemical in an environment surrounding
the non-specific chemical sensor in a pattern of responses which
are correlated to a first chemical suspected of being related to an
increased risk for developing lung cancer in the patient. In some
examples, the monitoring apparatus may comprise a plurality of
non-specific chemical sensors which are connected to a neural
network for pattern recognition and calculation in real time. In
still further examples, small deep-neural nets, which may comprise
as little as a half a megabyte of memory may be used for an
embedded system comprising a deep-neural net to recognize the
patterns of chemical arrays in real time and detect multiple
component systems.
[0012] In an example, the system may include examples where the
first chemical is radon. In an example, the system may include
examples where the first chemical is bis(chloromethyl) ether. In an
example, the system may include examples where the first chemical
is of a family of polycyclic aromatic hydrocarbons. In an example,
the system may include examples where the non-specific chemical
sensor comprises a polymer film doped with chemical species that
modulate the absorbent properties of a surface of the polymer film.
In an example, the system may include examples where the
non-specific chemical sensor comprises crystals whose natural
oscillation frequency is modulated by absorbance of materials onto
surfaces or onto films applied to surfaces of the crystal. In an
example, the system may include examples where the non-specific
chemical sensor detects biomarkers of lung cancer in the breath of
the patient.
[0013] In one embodiment, the system may include examples where the
first sensing device is a particulate sensing device. In an
example, the system may include examples where the first sensing
device senses at least a first biological agent. In an example, the
system may include examples where the biological agent is
Mycobacterium tuberculosis.
[0014] In another embodiment, the system may include examples
additionally comprising a personal sensing device that senses the
immediate environment surrounding the patient. In an example, the
personal sensing device senses radioactivity. In an example,
personal sensing may include chemical exposure sensing. In an
example, the personal sensing may include particulate exposure
sensing. In an example, the personal sensing may include blood
sensing. In an example, the personal sensing may include sensing of
a biometric. The biometric may be inhalation rate or the patient's
pulse in some examples.
[0015] In some embodiments, the personal sensor may be located
within the patient's lung. This personal sensor may sense chemical
markers. In some examples, this personal sensor may sense exposure
to environmental chemicals. In some other examples, this personal
sensor may sense radioactivity.
[0016] In some examples a system may be created for detecting a
form of cancer where the system include a means for obtaining
genetic data of a patient to determine variation at target
locations of the patient's genome, wherein the variations are
related to an increased risk of having the form of cancer. The
system may also include a first database record, wherein the first
database record contains records of familial health history. In
some examples, the database records of familial health history may
be dynamically updated. The system may also include a second
database record, wherein the second database record contains one or
more of a null dataset and a record of an environmental exposure of
the patient. Hereto the database record of environmental exposure
may be dynamically updated based on data obtained by the system as
well as data communicated to the system over networks. The system
may include a first sensor system, wherein the first sensor system
is configured to sense biomarkers related to a cancer state,
wherein the biomarkers emanate from the user. The system may also
include a second sensor system, wherein the second sensor system is
configured to sense the local environment of the user for one or
more of particulate matter and chemical pollutants. These elements
of the system may also be linked to an included processing system.
The processing system implements at least one of: a first algorithm
and a second algorithm. The first algorithm may include an example
which processes data from the first sensor system to compare a
first sensor system result to a threshold level, wherein the
threshold level is determined based on one or more of a result of
the determined variation at target locations of the patient's
genome, processing of data within the first database record, and
processing of data within the second database record. The second
algorithm may process data from the second sensor to determine
environmental conditions at the patient's location. The system may
also include a feedback device configured to communicate a signal
to the patient based on the results of processing by the processing
system. Thus when the system detects conditions of interest or
concern to a user a communication of the conditions may be made
with the user.
[0017] Implementations may include various methods. In an example,
a method of reducing a risk of acquiring lung cancer of a patient
predisposed to acquiring lung cancer may include various steps. The
method may include determining the predisposition of the patient to
acquiring lung cancer by analyzing the patient's genome. The method
may include installing a first sensing device wherein the first
sensing device is installed in a location of the home of the
patient. The method may include installing a second sensing device
wherein the second sensing device is installed in a location of the
work location of the patient; and the method may include installing
a processing system, wherein the processing system performs a first
algorithm which processes stored data originating from the first
sensing device and originating from the second sensing device and
determines a status to a threshold level, wherein the threshold
level is determined based on a result of the determined variation
at target regions of the patient's genome. The method may also
include installing a feedback device, wherein the feedback device
communicates a signal to the patient based on the status to the
alarm level. The method may include monitoring a first
environmental status at the home of the patient with the first
sensing device. The method may include monitoring a second
environmental status at the work location of the patient with the
second sensing device. The method may include detecting a signal
from one or more of the first sensing device or the second sensing
device, wherein the signal exceeds the threshold level. The method
may include communicating a signal to the patient based on the
detected signal. And, the method may include taking an action to
reduce the exposure of the patient to one or more of the first
environmental status or the second environmental status. The
various method steps may include the various options as have been
described in relationship to the system previously.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The foregoing and other features and advantages of the
invention will be apparent from the following, more particular
description of preferred embodiments of the invention, as
illustrated in the accompanying drawings.
[0019] FIG. 1 illustrates an exemplary model of pre-disposition to
lung cancer and exposure to environmental agents and the combined
effects on the chance to develop lung cancer in accordance with the
present invention.
[0020] FIG. 2A illustrates exemplary environmental sensing location
types in accordance with the present invention.
[0021] FIG. 2B illustrates exemplary individual sensing modalities
in accordance with the present invention.
[0022] FIG. 3A illustrates an exemplary multichannel broad-spectrum
sensing device in accordance with the present invention.
[0023] FIG. 3B illustrates exemplary results that individual
elements of a device from FIG. 3A may produce upon exposure to
environmental agents in accordance with the present invention.
[0024] FIG. 4 illustrates an exemplary particulate-sensing device
in accordance with the present invention.
[0025] FIG. 5A and 5B illustrate an exemplary colorimetric device
for sensing biological agents in accordance with the present
invention.
[0026] FIGS. 6A and 6B illustrate an exemplary sensing device for
biological agents in accordance with the present invention.
[0027] FIG. 7A illustrates an exemplary spectral technique for
generating an absorption spectrum in accordance with the present
invention.
[0028] FIGS. 7B, 7C and 7D illustrate exemplary devices that may be
useful for performing the technique of FIG. 7A in accordance with
the present invention.
[0029] FIGS. 8A-8E illustrate exemplary personal sensing devices
that may be useful for detecting biomarkers of patients related to
lung cancer in accordance with the present invention.
[0030] FIG. 9 illustrates exemplary method steps that may be useful
in treatment and prevention of lung cancer in patients in
accordance with the present invention.
[0031] FIG. 10 illustrates additional exemplary method steps that
may be useful in treatment and prevention of lung cancer in
patients in accordance with the present invention.
[0032] FIG. 11 illustrates exemplary method steps that may be
useful in treatment and prevention of lung cancer in patients in
accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0033] Although shown and described in what is believed to be the
most practical and preferred embodiments, it is apparent that
departures from specific designs and methods described and shown
will suggest themselves to those skilled in the art and may be used
without departing from the spirit and scope of the invention. The
present invention is not restricted to the particular constructions
described and illustrated, but should be constructed to cohere with
all modifications that may fall within the scope of the appended
claims.
[0034] Methods of forming and using sensing elements to diagnose
and treat lung cancer states and potentially delay or prevent their
development are disclosed in this application. A simplified model
of the general nature of the acquisition of lung cancer in a
patient may be that the likelihood of acquisition is a function of
an individual's root propensity for a type of lung cancer which
intersects with an exposure to an environmental contributor. Thus,
there may be examples of individuals who have a low propensity to
obtaining a form of lung cancer who are exposed to high levels of
an environmental contributor, such as a volatile chemical, and
never acquire a lung cancer. It is possible that other individuals
who have a high propensity to acquire a type of lung cancer may get
that lung cancer while seemingly having nearly no exposure to
particular environmental contributors.
[0035] Advancements in chemical sensing technology and
environmental sensing technology, particularly advancements that
have gone on over the past decade and continue today, when coupled
with advances in genomic mapping and the understanding of genetic
contributions to various forms of lung cancer allow for novel
treatment methods which are preventative, diagnostic and
therapeutic.
Glossary
[0036] In the description and claims below, various terms may be
used for which the following definitions will apply:
[0037] "Biocompatible" as used herein refers to a material or
device that performs with an appropriate host response in a
specific application. For example, a biocompatible device does not
have toxic or injurious effects on biological systems.
[0038] "Coating" as used herein refers to a deposit of material in
thin forms. In some uses, the term will refer to a thin deposit
that substantially covers the surface of a substrate it is formed
upon. In other more specialized uses, the term may be used to
describe small thin deposits in smaller regions of the surface.
[0039] "Functionalized" as used herein refers to making a layer or
device able to perform a function including, for example,
energization, activation, and/or control.
Genetic Predisposition to Lung Cancer and Environmental Factors
[0040] Studies have shown that significant incidence of occurrence
of lung cancer may be modeled as an interaction between an
individual's genetic predisposition with the amount and nature of
that individual's exposure to various environmental factors. For
example, one of the largest current environmental factors related
to many individual's acquiring of lung cancer is their smoking of
tobacco products. Yet, anecdotal evidence is commonly known that
there are cases of individuals who smoked large amounts of tobacco
products during their lives but never acquired lung cancer as well
as individuals who never smoked themselves but acquired lung cancer
nevertheless. Therefore, for some portions of acquired lung cancer,
a model 100 such as that depicted in FIG. 1 may be apropos. As FIG.
1 illustrates, an individual's chance of acquiring lung cancer may
be plotted as a line, for example, at an illustrative 50% chance
level 150 across dimensions of exposure to environmental agents 130
versus an individual's propensity to develop lung cancer 140. Where
movement above the line may increase the chance of lung cancer 110
and movement below the line may increase chance of non-cancer 120.
Thus, as development of knowledge about how genetic mutations and
inherited genetic anomalies may create predisposition to lung
cancer, strategies and equipment may be developed which may allow
individuals to monitor their exposure to various environmental
agents. Thus, when a patient's history and makeup lead a physician
to perform genetic testing to assess his genetic predisposition, a
patient may learn he has an elevated or even a high level of
"propensity" or predisposition to acquisition of lung cancer. In
the model 100, a patient with an elevated or high propensity will
have a profile for his or her chance of developing lung cancer as
illustrated at the right hand side of the chart. Thus, if a patient
can minimize or eliminate his or her exposure to important
environmental agents, that patient may significantly improve his
chances of not acquiring lung cancer. Thus, investment into sensing
equipment and the effort to control sensed exposures may create
significant improvements in outcomes.
[0041] There may be numerous variations in certain known genes that
relate to the determination of genetic propensity. However, this
knowledge is ever improving, and the spirit of the discussion
herein is meant to embrace inherently flexible adoption of new
knowledge as it becomes developed. The same flexibility may be
accorded to the development of knowledge about important
environmental agents that may be important for a patient with
elevated or high propensity to avoid. Nevertheless, there may be
important genetic variations that are currently suspected as
increasing genetic propensity for lung cancer. For example, one of
the important areas of genetic variation that has been focused upon
is polymorphic variation at genetic location 5p15.33
(TERT/CLPTM1L), at genetic location 6p21.33 (BAT3/MSH5) and at
genetic location 15q25.1 (CHRNA5/CHRNA3/CHRNB4) in patients of
European background. Additionally, single-nucleotide polymorphisms
(SNPs) at genetic location 22q12 (10,11) and the 15q15.2 locus
containing the TP53-binding protein 1 gene have been associated
with lung cancer risk. In patients of Asian background there may be
three additional susceptibility regions of focus at genetic
locations 13q12.12, 22q12.2 (15) and 3q28 (16). Whereas tobacco
smoking is the predominant risk factor for lung cancer, there are
several lines of evidence to suggest that genetic susceptibility
modulates this risk. Investigators working on the European
Prospective Investigation into Cancer and Nutrition (EPIC) have
identified several intriguing loci with more common population
frequencies. At the previously mentioned chromosome 15q25, is a
locus that contains several nicotinic acetylcholine receptors. Some
results of these studies have shown variants at the previously
mentioned 5q15.33, a region containing the hTERT and CLPTM1L
genes3, hMSH5 in the chromosome 6 MHC region 1, RAD52, and
CDNK2A4.
[0042] In a high proportion of these mentioned genetic loci are
varients that also show relevance to a particular histology (MHC,
CDKN2A, RAD52, hTERT), which may suggest that for lung cancer,
histological subtype may be important. As mentioned, there may be
other genes and variations that are known or yet to be known that
may be probed for with genetic testing to assess an individual's
propensity to acquire lung cancer. Methods may probe for these
various genetic variations and, in a semi-quantitative manner, the
results may be used to classify a patient's risk profile into
numerous strata, such as low, elevated and high propensity for
pre-disposition to lung cancer. Any of the commercially and
scientifically viable means to determine genetic variation in
targeted gene loci may be applied to samples of genetic matter from
patients to determine a relative level of pre-disposition risk to
lung cancer.
[0043] A system related to the present invention may include
devices that may measure or monitor genomic data for disposition
risk to lung cancer. A sample from a patient may be processed with
a thermal cycler for performing genetic amplification, wherein the
result of the genetic amplification is used in subsequent steps for
determining a sequence of DNA of a patient to determine variation
at target regions of a patient's genome. Important regions to
screen for mutation may be assessed to determine the risk.
[0044] In similar models, devices which are used to monitor a
patient's environment, such as a smart phone equipped with
monitoring devices, may in turn include an application which
performs the monitoring, and also includes a capability to access
data across an internet connection. In some examples, a patient may
have submitted a sample of his genetic material to a commercial
organization who sequences various locations of the patient's
genome and records the results in a database. The application may
have access to the data or may receive communication from the
commercial organization which accesses the data and passes
identification of genetic modifications of interest to the
application on the smart device, which may alter or supplement its
analysis conditions based upon the identified genetic
modifications. In some examples, the commercial organization or
another organizations database may include aspects of an
individual's family health history. If the Patient activates
appropriate means of "opting-in" to receiving such family health
and genomic history, the smartphone application may also receive
such data in concentrating its analysis. In an example, a record of
a family member may indicate an occurrence of a particular type of
cancer which population analysis may be correlated to sensitivity
to specific environmental agents and conditions which may be
monitored by the monitoring apparatus. Given a specific sensitivity
resources of the analytical device may be prioritized and/or
dedicated to the analysis of the particular environmental agent or
condition.
[0045] Similarly, as depicted in the exemplary model of FIG. 1,
there are numerous general environmental aspects and agents that
may be associated with increased chance of acquisition of lung
cancer. As the knowledge of important genetic variations to use to
gage propensity may be increased, the ability to identify even
further important environmental agents may increase as well.
Currently, it may be widely accepted that tobacco smoke is an
environmental agent of acute importance to lung cancer that may be
important if the patient is a primary smoker as well as an
individual exposed to second-hand smoke.
[0046] Other environmental agents may include exposure to radon
gas. Radon is produced by the natural breakdown of uranium in soil,
rock and water that may eventually become part of the air a patient
may be exposed to. Radon is of particular importance because of its
prevalence in many areas of the world. For example, in homes having
basements, radon contamination over a long period of time may pose
a health risk.
[0047] In some examples, asbestos and other fibrous silicon
containing compounds may be important environmental agents to
track. Other materials that may be common in the workplace include
elemental compounds containing arsenic, beryllium, cadmium,
chromium and nickel. Many of these environmental agents can be
compounded in importance when they occur in multiple types of
exposure.
[0048] Air pollutants related to the combustion of diesel and other
fossil fuels as well as other chemicals such as bis(chloromethyl)
ether and polycyclic aromatic hydrocarbons may also be important
environmental agents that increase risk of developing lung
cancer.
[0049] In some examples, infectious agents such as tuberculosis may
be important environment agents of exposure which can increase the
chance of acquisition of lung cancer.
[0050] Exposure to small particulate matter of many different
elemental compositions may also be important environmental exposure
risks to patients. This particulate matter, which shows increased
risk factors for lung cancer may be summarized into at least two
buckets. The PM2.5 (particulates found in the air whose size is 2.5
microns or less) and PM10 (particulates found in air whose size is
10 microns to 2.5 microns) are measured parameters that may be
correlated to risk of lung cancer development. The risk factors may
be similar for different types of lung cancer such as squamous cell
and adenocarcinoma, and the risk factors may be modulated based on
the life history of patients relating to whether they are a smoker,
a past smoker or someone who has never smoked.
[0051] There may be numerous agents within various types of smoke
that relate to risk of lung cancer acquisition. Amongst the
components of various types of smokes, particulates that are even
finer than the micron scale may be called nanoparticles and may be
important risk agents. The development of commercial products with
engineered nanoparticles is an emerging product type which may
change aspects related to occupational and personal exposure over
the coming decades. Numerous types of sensors may be able to
monitor for particulates and for nano-scale particulates, as will
be discussed in later sections. A unique feature of nanoparticles
is that they have a very large surface area to mass ratio. Thus,
effects of exposure to them might be more related to surface area
than mass.
[0052] Although there may be no epidemiological evidence from human
studies which conclusively demonstrates a lung cancer risk
association with nanoparticle exposure, early evidence from
experimental toxicity studies may suggest potential cause for
concern. Thus, methods of monitoring such materials for patients
with high pre-disposition to lung cancer may be prudent.
Exemplary Sensing Devices
[0053] As has been mentioned, it may be advantageous to monitor air
related to environments that people, or in particular people with
high predisposition to lung cancer, may breathe. Referring to FIG.
2A a summary of the different types of environments that may be
monitored is shown in exemplary form.
[0054] A person may spend an appreciable portion of their time in
residence 202. Thus, various rooms may be equipped with various
sensing equipment such as particulate monitors, specific chemical
monitors, radioactivity monitors such as for radon, biological
sensors, and broad-spectrum monitors that may be sensitive to
various types of chemical and particulate forms. These types of
sensors are described in more detailed form in subsequent sections.
Different rooms in a house may have one or more of these types of
sensors located. Bedrooms, kitchens, and living rooms may provide
focal locations for sensing, but other locations such as in the
basement and/or garage may also emerge in importance.
[0055] A person may spend time in their outside environment 203. An
outside environment 203 may include confined spaces that are not at
a home or workplace and may, therefore, include the interior space
of an automobile for example. As well, external environments such
as parks, walking paths, yards, decks and the like may be
frequented locations where the air quality may be important for
patients with a pre-disposition to lung cancer. Municipalities, and
state agencies may establish regional monitoring stations for
sensing of various kinds, including particulate matter, and the
chemical nature of air pollution. In some examples, the real-time
or near-real-time sensing output of such monitoring may be
communicated via delivery means such as the internet and wireless
communication. So-called "Smart Cities" may have a plurality of
sensors deployed in urban areas where the sensors act as Internet
of Things (IoT) devices which have a small power source which may
be rechargeable, the sensing means, and a communication capability
to interface with the internet or other networks. In some examples,
a method according to the present invention may include apparatus
and algorithms that access internet distributed databases that
contain quality measure related to external air environments. The
results of a number of sensors, which may be geographically
separated on the scale of a human being may none the less be used
to interpolate regionally averaged exposure estimates to a variety
of environmental agents that may be of concern to lung cancer
patients or patients with elevated or high pre-disposition to lung
cancer.
[0056] Communications between a plurality of sensors may be able to
be formed into different types of network topologies. In some
examples, a plurality of mostly stationary sensors with
communication capabilities may be arranged into wireless mesh
networks. In some examples, stationary network nodes may interact
with wireless nodes to form a complex network topology. The various
distributed sensors may be useful for monitoring environmental
conditions while at the same time participate in forming, amongst
themselves, robust fault tolerant networks where data communication
can be facilitated and made very efficient. Thus a system of
environmental monitoring sensor systems, distributed to roughly
stationary and reasonably dense locations may form a meshed network
base that may support other mobile nodes that enter into the mesh
environment. Thus patients who wear monitoring devices that can
link to the local environmental sensing mesh network may be able to
link to the sensing systems while also providing data themselves.
Systems distributed amongst numerous patients/users may likewise
participate or assemble with wireless mesh form networks.
[0057] External environments that are themselves contained, such as
automobiles, as mentioned previously may have internal sensors that
monitor the quality of the air within the contained environment. In
some examples, automotive devices may have smart devices
incorporated that may interface with the internet and access
information related to the environmental air quality measured by
sensing devices. The resulting database interpolations may be used
to plan and execute routing decisions for pre-disposed patients as
they are transported from one place to another. In some examples,
they may be able to warn the patient that the terminus of the
planned route is projected to be experiencing an increased level of
an environmental agent of interest. Such information may be useful
to change the planned transportation. In some examples, the patient
may be delivered to a terminus via an internal parking garage for
example. In other examples, the patient may not travel to the
terminus entirely. And, in other examples, the patient may employ a
number of air purification strategies such as particulate filters
and chemical/absorbent material filters. In still further examples,
the estimated exposure of the patient based on sensors in a closed
environment or regional sensor networks may be associated in a
database of the patient as an accumulated exposure estimate. In
some examples, devices that can track the geolocation of
individuals as they move from place to place may be useful in
providing improved accuracy of regionally estimated exposures as a
patient moves through a region.
[0058] Referring again to FIG. 2A, an individual's place of work
204 may have monitoring systems deployed for the purpose of
monitoring the airspace for all stakeholders at the location, or in
some examples to monitor the air space for individuals with
elevated pre-disposition to lung cancer. Buildings may be equipped
with various sensing equipment such as particulate monitors,
specific chemical monitors, radioactivity monitors such as for
radon, biological sensors, and broad-spectrum monitors that may be
sensitive to various types of chemical and particulate forms. As
well, in work places there may be much higher likelihood of
exposure for certain types of materials such a volatile organic
carbon gasses, many forms of particulates and aerosolized metal
containing compounds. Sensors that have been trained to detect the
chemicals that are brought to the work place or that are likely
byproducts of processes that are occurring in the work place may be
specifically installed.
[0059] In nearly all of these environments and any others that may
be on the interface between these types of environments, a patient
may employ personalized sensing equipment 201. There may be
numerous types of equipment that have sensors included in them and
are associated with a user either by being a wearable sensor such
as a smart watch or by being associated with an appliance that a
user will tend to keep with them such as a cell phone, as
non-limiting examples. Personal sensors may be equipped with
various sensing equipment such as particulate monitors, specific
chemical monitors, radioactivity monitors such as for radon,
biological sensors, and broad-spectrum monitors that may be
sensitive to various types of chemical and particulate forms. In
some examples, a sensing device may include a number of these
different sensing capabilities. In some other examples, a plurality
of devices may be used to perform different sensing tasks. The
personalized sensing equipment 201 may be chosen or "trained" for
non-specific sensing equipment to monitor the near environment of
the patient in a nearly real-time manner.
[0060] In some examples, the monitoring apparatus may comprise a
plurality of non-specific chemical sensors which are connected to a
neural network for pattern recognition and calculation in real
time. Artificial neural networks (ANNs) or connectionist systems
are computing systems inspired by the biological neural networks
that constitute animal brains. Such systems learn (progressively
improve their ability) to do tasks by considering examples,
generally without task-specific programming. For example, in image
recognition, they might learn to identify images that contain cats
by analyzing example images that have been manually labeled as
"cat" or "no cat" and using the analytic results to identify cats
in other images. They have found most use in applications difficult
to express with a traditional computer algorithm using rule-based
programming. A neural network as used herein, which may also be
called and artificial neural network when not involving biological
neurons, is based on a collection of connected units called
artificial neurons. The connections between the connected units may
be called synapses and they can be used to transmit a signal from
the first neuron to another neuron. The receiving neuron can
process the signal(s) and then signal downstream neurons connected
to it. Neurons may have "state" defined. The state may be
represented by a value which may typically be represented between 0
and 1. As learning occurs with a system of synapses and neurons,
the weighting factor that a neuron is given may vary. By varying
the weighting, the system can adjust the strength of a signal that
is communicated downstream.
[0061] A deep neural network is an artificial neural network with
multiple hidden layers between the input and output layers. Deep
neural networks can model complex non-linear relationships which
may relate to the signals that non-specific sensor arrays generate
particularly when combinations of analytes are present in the
environment. A deep neural network may be used on arrays of sensors
and may create architectures which generate models for the complex
superposition of signal patterns for different combinations of
analytes which improve in accuracy over time or "learn". The extra
layers of a deep neural net may enable composition of features from
lower layers, potentially modeling complex data with fewer units
than a similarly performing shallow neural network. In still
further examples, small deep-neural nets, which may comprise as
little as a half a megabyte of memory may be used for an embedded
system comprising a deep-neural net to recognize the patterns of
chemical arrays in real time and detect multiple component systems
in small form factors that can be incorporated in portable smart
devices or biomedical devices. A sensing device with neural network
processing components may be trained with standard mixtures of
analytes to create an accurate sensing device that may function
rapidly or may function in real time.
[0062] In some examples, the personalized sensing equipment 201 may
be connected to devices capable of algorithmically processing the
data associated with the sensing equipment. The devices may be
enabled with warning trigger levels such that when a sensing device
begins to see an elevated response to a monitored environmental
agent it may communicate to the user a need to take an action. The
means to communicate to the user may include any standard
communication protocol, including in a non-limiting sense, an
alarm, buzzer, vibration or visual screen display which alert the
patient to an environmental condition that motivates him or her to
take an action. The action may include evacuating the location or
wearing a piece of protective apparel as non-limiting examples. In
some examples, the connected device may maintain a database which
records the various sensor outputs along with a time date stamp.
The recorded data may be aggregated in various manners that may
support decisions related to treatment of a patient. In some
examples, evidence of elevated exposure events or integrated
exposure amounts over time or combinational exposures (where more
than one sensed exposure occurred simultaneously) may be used to
elevate screening protocols such a x-ray analysis, blood monitoring
or other such examples of medically appropriate screening for
patients with a high or elevated pre-disposition to lung
cancer.
Individual Sensing Examples
[0063] Referring to FIG. 2B, an exemplary illustration of numerous
personalized sensing equipment examples is depicted. Included in
the illustration are numerous devices that may be used to sense
exposure to environmental agents. In some other devices, the
purpose may be to monitor systems of the patient for evidence
within the body of focused environmental agents, or metabolites of
such focused environmental agents. In still further devices, the
purpose of some of the monitor systems may be to sense the presence
of biomarkers that may be correlated to the presence of a lung
cancer disease state.
[0064] Some of the devices may operate in a manner that may
indicate whether the patient has been exposed to pathogens of
interest. In a non-limiting sense, Tuberculosis may be an example
of a pathogen that has potential causative relationships with lung
cancer in some infected individuals. Devices which can sense the
presence of exposure to Tuberculosis, perhaps even before an
infection has taken place may be of import. In some other examples,
biometric information that may be indicative of a state of
infection such as temperature, impaired or "noisy" breathing or
other such metrics may be useful.
[0065] Still further devices may record biometric data that may be
used to connect the physiological state of a patient during an
exposure event. For example, pulse rate, breathing rate, breathing
volume, and blood pressure may be useful biometrics to
understanding the nature of uptake of an environmental agent that a
patient may be exposed to.
[0066] There may be numerous types of biomedical related sensing
techniques that may be used individually or in combinations to
perform sensing of an individual consistent with the present
invention. Referring again to FIG. 2B, a summary of numerous
exemplary types of biomedical devices may be found. Various
ophthalmic devices 200, such as contact lenses, intraocular
devices, punctal plugs, and the like may perform various sensing
functions including analyzing analytes in the biofluids in the
ocular environment. Tear fluid may contain chemicals and materials
contributed from the body of the individual, but they also are
significantly exposed to the environment of the individual and may
contain a historical exposure record for a time period.
[0067] Contact lenses, 210 may also be used to read and quantify
results from sensing devices that may be implanted into ocular
tissue.
[0068] Implants into organs 205, may include brain implants, heart
implants, pacemakers, and other implants that are implanted into
organs of the user. These implants may be able to directly sense or
indirectly sense a user's cellular tissue layer or a fluid
contacting a user's cellular tissue layer. A specialized type is
described with reference to a lung implant 295 as is discussed in
greater detail subsequently.
[0069] In other examples, a biomedical sensing device may be an
aural sensor 220. The aural sensor 220 may indirectly sense a
biometric such as temperature as an infrared signal for example.
The aural sensor 220may also be able to quantify other biometrics
such as blood oxygenation, analyte and bio-organism sensing and
other such sensing. They also may be used to sense chemical
emissions from the individual as well as environmental chemicals
and materials in the space of the individual. Some biometrics may
have potential diagnostic relevance in the detection of insults and
challenges on the biome of an individual in his or her environment,
or the biometrics may have diagnostic relevance to disease
states.
[0070] A dental sensor 230 may be used to sense a variety of
different types of biometric data. The sensor 230 may probe the
fluids in the oral cavity for biomolecules and chemical species
from food, and the biological fluids affected by environmental
exposures of various kinds. The sensor 230 may also probe for
indirect measurements of various types including in a non-limiting
perspective pressures, temperatures, flows and sounds in the
environment that may be directly or indirectly related to
biometrics such as body temperatures, breathing rates, durations,
strengths and the like. In addition, the dental sensor 230 may be
utilized to sense biometric data during both inhalation and
exhalation. Such a dental sensor may comprise non-specific sensors
with neural net based control and/or analysis of data obtained from
the sensor. In some examples a chemical separation membrane may
allow volatile organic compounds to pass into a sensor while
excluding aqueous based liquids. Polymers of Intrinsic
Microporosity (PIM-1) based membranes made with designed
combinations of block copolymers, which have micropores to allow
permeation of gasses, may provide examples. Other examples may
include polymers with intrinsic porosity such as polyacetylenes,
fluorinated polymers, polynorbornanes, and polyimides as
examples.
[0071] Vascular port sensors 240 may be used to sense various
aspects within a blood stream. Some examples may include neuronal
proteins or other hormones or antibodies that may be expressed
during early stages of lung cancer and may be related to
paraneoplastic syndrome. Any sensing example that interacts with
bodily fluids that may contain these neuronal proteins or other
hormones or antibodies that may be expressed during the early
stages of lung cancer may operate in this manner and such examples
are not meant to be limited to vascular port sensors 240. Other
examples of sensing with a vascular port sensor 240 may be oxygen
monitoring or other chemical monitoring. Other biometrics may be
monitored at a vascular port such as blood pressure or pulse as
non-limiting examples.
[0072] Some biometric sensors may be wearable sensors 250. A
wearable sensor 250 may indirectly measure a variety of biometrics
as well as chemicals and materials in the environment as well as
those emitted by the individual. A well-known example is the sweat
chloride assay for cystic fibrosis, a very serious lung disease. In
this assay, sweat is collected from the individual and certain
biomarkers are tested for. More specifically, the cystic fibrosis
transmembrane conductance regulator (CFTR) gene located on the long
arm of chromosome 7 (7q31.2) is examined. In some examples, the
sensing element may be independent of any body tissue or body fluid
of a user. Such a sensing element may monitor biometrics related to
the user's body as a whole, or the chemical and particulate
environment of the individual. In some examples, such devices may
have geo-locating devices within them that may contain a record of
where the individual has been over time. Such information may be
married with data in external databases to infer levels of
exposures of individuals. Other wearable sensors may directly or
indirectly sense or probe a user's cellular tissue layer which may
allow measurements of temperature, oxygenation, and chemical
analysis of perspiration as non-limiting examples. The wearable
sensors 250 may take the form of or be incorporated into clothing
or jewelry in some examples. In other examples the wearable sensors
250 may attach to clothing or jewelry.
[0073] Various examples of biometric sensors may be incorporated
into sub-cutaneous sensors 260 where a surgical procedure may place
a biomedical device with sensors beneath a skin layer of a user.
The sub-cutaneous sensor 260 may be sensitive with direct contact
to tissue layers or to interstitial fluids. The sub-cutaneous
sensor 260 may be able to analyze for various analytes, for
example, with techniques described previously herein. Physical
parameters may also be measured such as temperature, pressure and
other such physically relevant biometric parameters.
[0074] Sensors may be incorporated into blood vessels or
gastrointestinal stents of various kinds forming a stent sensor
270. The stent sensors 270 may therefore be able to perform sensing
of various chemical species. Stent sensors 270 incorporated within
blood vessels may be able to also characterize and measure physical
parameters of various types. For example, a blood vessel form of
stent sensor 270 may be able to measure pressures within the vessel
during heart pumping cycles for a physiologically relevant
determination of blood vessel pressure. There may be numerous
manners that such a pressure sensor could function with small
piezoelectric sensors, elastomeric sensors and other such sensors.
There may be numerous physical parameters in addition to pressure
that may be monitored directly within the blood stream. Chemicals
including hormones as have been mentioned previously that may be
relevant to a lung cancer state may be monitored as well.
[0075] A pill form biometric sensor, such as a swallowable pill 290
may be used to provide biometric feedback and may sense simple
chemicals and bio-chemicals in an individual. In some examples, the
swallowable pill may incorporate pharmaceutical components. In
other examples, the swallowable pill 290 may simply contain
biometric sensors of various kinds. The swallowable pill 290 may
perform analyte measurements of the gastrointestinal fluids that it
incorporates. Furthermore, the pills may provide central core
temperature measurements as a non-limiting example of physical
measurements that may be performed. The rate of movement of the
pill through the user's digestive track may also provide additional
information of biometric relevance. In some examples, analyte
sensors may be able to provide measurements related to dietary
consumption and nutritional aspects. Since inhaled chemicals and
particulate matter traverses the mouth, throat and larynx, some
record of exposure may proceed through saliva into the
gastrointestinal tract where such a sensor may record their
presence.
[0076] A bandage form sensor 280 may be used to perform biometric
and environmental sensing. In some examples, the bandage form
sensor 280 may be similar to a wearable sensor 250 and perform
measurements upon chemicals in the skin environment including
aspects of perspiration as well as incident chemical and material
exposure analysis. The bandage form sensor 280 may also perform
physical measurements. In some special examples, the bandage may be
in the proximity of a wound of various kinds of the user, and the
chemical and physical measurements in the region may have a
specialized purpose relating to healing. In other examples, the
bandage sensor 280 may be a useful form factor or environmentally
controlled region for the inclusion of an environmental exposure
sensor.
[0077] As stated above, a biometric sensor may be incorporated
within a lung implant 295. A lung implant may be made into the lung
epithelial tissue of a user in some examples where it may have an
active or passive (sensing) role. Biometric sensors incorporated
within the lung implant 295 may allow for chemical and physical
monitoring. In some examples, a lung implant 295 may be used to
sense biomarkers of lung cancer types. In an alternative sense, a
lung implant 295 may give a means to monitor directly environmental
chemical, particulate and other materials that have made their way
to the lung tissue.
[0078] The biometric sensor types depicted in FIG. 2B may represent
exemplary types of sensors that may be consistent with the present
invention. There may be numerous other types of sensors that may be
consistent with the present invention however. Furthermore, there
may be examples of sensors that combine some or all the functional
aspects discussed in relation to FIG. 2B which may be relevant. The
present invention is not meant to be limited to those examples
provided in FIG. 2B. It is important to note that the various
sensors are illustrated at certain locations but may be at any
location on the body depending on specific application aspects.
Non-Specific Chemical and Material Sensors
[0079] A class of sensing devices has been developed which sense
the presence of chemicals in non-specific ways. There may be a
number of means to accomplish this sensing. In an example, a set of
shaped quartz crystals are coated with different substances such as
polymers, monolayers of inorganic materials and biological
antibodies as non-limiting examples. These different substances
will have a unique bonding aspect to molecules in their
environment. And in the case of antibodies, may be relatively
specific to biological materials with certain shapes. Molecules in
the environment of the sensor may adsorb onto the crystal surface
and find a binding site where they may settle down. The presence of
many bonded molecules on the surface layers of the crystal change
the resonant frequency that the quartz crystal will oscillate at.
By forcing the quartz sensors into oscillation, the resonant
frequency shift of the crystal may be measured and physical
principles allow for a relative calculation of the mass change of
the crystal to be calculated. Different molecules may adhere to the
various coatings in different yet characteristic manners. The
different characteristics allow for a collection of different
crystals to have the ability to distinguish different molecules,
particularly when they have significantly different characteristics
across the different surface types.
[0080] It is important to note that many different types of
chemical sensors are known. For example, mass spectrometers and gas
chromatographs may be adapted for use in accordance with the
present invention.
[0081] Referring to FIG. 3A, an exemplary collection of thirty or
more of the crystals assembled into a "Chip" form 300 with
electrical contacts to probe and measure frequency difference of
the crystals for different amounts of absorbance of materials from
the gas phase is illustrated. A common or ground connection 310 may
connect one side of a first crystal 321 which may have a second
connection 320 to apply electrical signals across the first crystal
321 to probe for its characteristics. A second crystal 331 may use
the common ground connection 310 to electrically connect one side
of the crystal and a second contact 330 distinct to the second
crystal to simultaneously record the characteristics of the second
crystal with exposure to an air sample.
[0082] When the "chip" 300 is to be used, it may be exposed to a
means to desorb any molecules from the surfaces of any of the
crystals. In a non-limiting example, the crystals may be
electrically heated to desorb the molecules. In some examples, the
sensing device may comprise two sets of chips, where one is used to
absorb and analyze gas samples and the other may be closed off from
sampling so that it may be heated to clear the sensing surfaces.
After the sensor cools down to an operating temperature the sensor
may begin to probe the air environment and molecules may absorb
onto the different crystal surfaces, and to register different
absorption signals with time. Referring to FIG. 3B, a collection of
exemplary responses of the thirty-two different crystals depicted
in FIG. 3A may be displayed 350 showing the calculated rate of
increase of mass for each of the different crystal types. The
exemplary first crystal type may have a first rate of increase of
mass depicted at 322 where the second crystal may have the result
depicted at 332. The results in FIG. 3B may indicate that a number
of different gaseous species at different concentrations may be
absorbing onto the crystal array. In some examples as a detection
array is utilized it may eventually be "fouled" by materials that
it is exposed to, whether the intended analytes or other molecules
or species in the environment. Thus, there may be cases where
single use apparatus may be desirable. Therefore, analytic
solutions may be implemented in a variety of ways, including as a
disposable array of encapsulated sensors configured for one-time
use or a disposable array that may be cleaned after one or more
uses.
[0083] The crystal array may have been "trained" on known
concentrations of known gas species to find the different responses
for each of the different sensors that can be stored into a
database. Algorithms may use these trained responses to analyze
dynamic responses of the non-specific sensor to air samples and
mathematically extract the highest probability gases that are
present in the air. The technique may work especially well for
conditions where a small number of the ambient gasses are changing
at a particular time or when there are only a few gasses that are
present.
[0084] In an exemplary sense, the mathematics of a combination of
sensors exposed to a collection of gases may be depicted as
follows. In the condition where the array of sensors behaves with
linear response curves and also demonstrates additive response to
analyte mixtures, then the response of a particular sensor to a
mixture of m analytes may be modelled as:
response=.SIGMA..sub.k=1.sup.mconcentration(k)sensitivity(k)
(1)
wherein concentration(k) represents the concentration("conc") of
the k.sup.th analyte and sensitivity(k) represents the
sensitivity("Sen") of the k.sup.th analyte on the particular sensor
site. The combination of an array of n sensors leads to a system of
linear equations that may be represented as
[ reponse ( 1 ) response ( n ) ] = [ conc . ( 1 ) conc . ( m ) ]
.times. [ sens ( 1 , 1 ) sens ( 1 , n ) sens ( m , 1 ) sens ( m , n
) ] . ( 2 ) ##EQU00001##
The resulting equations may be used to extract relationships for
expected concentrations of the unknown number of analytes in the
mixture. In many types of analysis, a greater number of sensors
increases the accuracy of extracted results, especially when the
sensing elements create significantly different responses across
the gases that are present in the mixture. It may also be true that
the greater the number of gases in the sample, the lower the
accuracy of the responses that may be calculated.
[0085] There may be a number of different types of sensing elements
that may be formulated to create non-specific sensing arrays of
large numbers of sensing elements. In some examples, polymer based
sensing elements may be variously doped with different compounds
that tailor the surface of the polymer to have different absorbent
properties to analytes. Large numbers of elements in small array
systems may be formed with the processing equipment of integrated
circuits for these type of polymer based sensor. In some examples,
changes in dielectric constant or effective dielectric thickness of
sensors that may occur when molecules bind to their surface may be
sensed as changes in the capacitive nature of the probe element.
For example, nanosheet-based field effect biosensors may be
utilized to detect cancer marker proteins, Hereto, different
binding to differently formulated surface layers which may be
coated with different materials or may have "dopants" of various
types implanted into the polymer sensing structures may create
different changes in the capacitive nature of probe elements upon
exposure.
[0086] Another type of sensing element, may be formed using carbon
nanotube tips. The tips may be electrically connected to a voltage
source that ramps the tips to form electric fields in the vicinity
of the tips and characterize the breakdown characteristics of
molecules in the gas phase. There may be other types of sensor
arrays that may be formulated that provide small low cost, reusable
sensing modules that may be used in the various environmental
sensing uses as have been described previously. Some sensors of
these types may also be able to characterize particulate matter,
particularly nano-particulates present in a gas sample.
Particulate and Dust Sensors
[0087] A patient with elevated or high pre-disposition to acquiring
lung cancer may monitor and control exposure to particulates in his
or her environment. For some of the smallest particulates such as
nano-particulates, some of the non-specific chemical and material
sensors may be sensitive to the binding of such nano-particulates
to its surface and may be able to detect their presence. Generally
other types of detectors may be used to detect levels of
particulates. Referring to FIG. 4, an exemplary particulate
monitoring apparatus is illustrated. A light beam is directed to a
flow of air 430 in a transparent tube 400 which concentrates the
air flow into a confined region. Particulates in the air flow such
as particulate 440 flow into the confinement region where a laser
light beam 420 from a laser light source 410 impinges on a
particulate and is scattered 470 by the particulate. When there is
no particulate in the beam path then the light will proceed through
the transparent tube 400 and is absorbed by the beam stop 460.
Thus, only light that is scattered 470 will pass by the beam stop
460 and on to a photodetector 450. In some examples, the
photodetector 450 will have multiple isolated sensing regions which
can discriminate an arc of scattering angles which may be used by
the particulate sensor to estimate the relative size of the
particulate that is scattering the light since the scattering angle
may be a function of the size of the particulate.
[0088] A light scattering particle counter may be formed into a
small portable sensing device that may be a wearable device. The
largest energy consumption of such a device may be the
incorporation of a pumping system or other air flow system which is
needed to move the various particulates through the sensing region.
For a wearable device, such a power source may be provided by a
battery.
[0089] In some examples, a light scattering particle counter may be
fixedly mounted in a particular location. The sensor may provide
sensor data on an autonomous basis to databases through internet
connectivity. In some examples, a particle sensor may be placed in
a work place near a patient with an elevated or high
pre-disposition to acquiring lung cancer. As well, a particle
sensor may also be placed within a home location.
[0090] When a wearable or fixedly mounted particle counter detects
an elevated level of particulate matter it can sound an audible
alarm. In some examples, the sensor may communicate its sensing
levels to servers through internet connections. Software algorithms
may be used to process the sensor data and in some examples may be
able to ascertain a location of a patient. If the patient is
located in a region around a sensor during a detection of elevated
particulates, a communication may be made to a device of the user
such as, in a non-limiting sense, a cellular phone or smart phone.
A pre-disposed patient may take protective actions based on
detection of elevated particulate levels in the air such as by the
wearing of protective apparel like filtering masks. In some
examples, a user may leave a location or avoid going to a location
when an elevated level of particulate matters is detected. By
taking such actions, a pre-disposed patient may lower their
cumulative exposure to environmental agents which may in turn lower
the risk level for his acquiring lung cancer.
[0091] Detection levels which are correlated to a known location of
the patient may also be communicated to databases which may store a
record of these exposure events. The cumulative exposure values and
the details of exposure events may be used by medical professionals
to motivate preventive actions such as enhanced screening of
patients with exposure to environmental agents.
Chemical Specific and Analytical Sensors
[0092] In some use environments, the use of chemical specific
sensors or sophisticated analytical sensors may be used to detect
chemicals known to be related to increased risk of obtaining lung
cancer. Some chemical specific sensors may use microfluidic
processing devices to perform chemical or electrochemical sensing
techniques to investigate air samples for the quantitative
evaluation of the gasses present including specific gasses of
interest for increased risk to pre-disposed risk patients.
Chemically selective field effect transistor based sensors may
provide selective response to the presence of selected chemicals in
gas or liquid samples. Electronic sensors based on the field-effect
transistor may provide an efficient and potentially low cost sensor
base that may be sensitive for various chemical and biological
analyte classes. A class of field effect transistors with active
channels comprising nanostructured semiconductors provides
particularly sensitive and effective field effect transistor-based
electronic sensors. Versions based on one-dimensional silicon
nanowires and carbon nanotube and two-dimensional graphene and its
derivatives are among the most promising channel materials in
electronic sensors. Absorbance of gas molecules upon the channel
regions of the field effect transistor create reproducible shifts
in the conductivity of the channels of arrays of field effect
transistors. The channels may be functionalized by various
treatments of the channel region materials to chemical
transformations, physical transformations and the like. A similar
variation in gas sensing devices may result from functionalized
metal oxide semiconductor (MOS) sensor arrays. Conductometric
semiconducting metal oxide gas sensors have been well studied and
characterized and constitute a desirable sensor type for the
inventive concepts herein. MOS sensor arrays are desirable for gas
sensing under atmospheric conditions due to the low cost and
flexibility in production as well as their simplicity in use. MOS
sensor arrays have been demonstrated to be able to sense large
numbers of detectable gases in numerous possible application
fields. In addition to the conductivity change of gas-sensing
material, the detection of this reaction can be performed by
measuring the change of capacitance, work function, mass, optical
characteristics or reaction energy released by the gas/solid
interaction. In some examples, an array of functionalized MOS
sensors in which the gate is modified/treated/functionalized to
have an affinity for certain molecules may operate to sense the
concentration of such adsorbed gas molecules by their modulation in
the work function.
[0093] In some examples, more sophisticated chemical sensing
equipment may be used for environmental sensing. Techniques such as
gas chromatography/mass spectrometry may provide highly accurate
and sensitive sensing protocols for a wide range of analytes. There
may be other techniques that provide analytical results with
relatively sophisticated testing protocols such as in a
non-limiting sense electrochemical sensors which may sense analytes
with voltammetry analysis, inductively couple plasma atomic
emission spectroscopy (ICP AAS) or mass spectroscopy (ICP MS) for
detection of metallic constituents, and various spectroscopic
technics such as gas chromatographic infrared spectroscopy (GC-IR)
for characterization particularly of volatile organic carbon
compounds. In some of these examples development activities for
small form factor devices are ongoing, but generally these
sophisticated techniques may have relatively higher cost factors
and may have larger form factors for deployed sensing devices. The
analytical techniques may be particularly suited for sensing of
regional air quality, the results of which may be shared with
databases and accessed by software algorithms to provide
communication and warnings to predisposed patients that are located
in the vicinity of such a system when it detects an elevated level
of chemicals. In some examples, there may be situations where
dedicated chemical sensors that are focused on limited or single
chemical species may be used either to monitor environments or to
analyze samples of breath of a patient. In some examples small
infrared based detectors may be configured to detect a specific
species or a combination of specific gases. The infrared signature
of a specific species may absorb light at characteristic
frequencies and with relative absorption rates. For certain
combinations of species, there may be enough discreteness of the
absorption spectra to allow for quantitative analysis of these
multiple species. Diffusion controlled electrochemical based sensor
are another example where an analysis system can be configured to
target accurate sensing of mostly single gas systems. A combination
of such specific sensors may provide a means of accurately
analyzing for the presence of a specific combination of gas
species.
Biomarkers/Analytical Chemistry
[0094] A biomarker, or biological marker, generally refers to a
measurable indicator of some biological state or condition. The
term is also occasionally used to refer to a substance the presence
of which indicates the existence of a living organism. Further,
life forms are known to shed unique chemicals, including DNA, into
the environment as evidence of their presence in a particular
location. Biomarkers are often measured and evaluated to examine
normal biological processes, pathogenic processes, or pharmacologic
responses to a therapeutic intervention. In their totality, these
biomarkers may reveal vast amounts of information important to the
prevention and treatment of disease and the maintenance of health
and wellness.
[0095] Biomedical devices configured to analyze biomarkers may be
utilized to quickly and accurately reveal one's normal body
functioning and assess whether that person is maintaining a healthy
lifestyle or whether a change may be required to avoid illness or
disease. Biomedical devices may be configured to read and analyze
proteins, bacteria, viruses, changes in temperature, changes in pH,
metabolites, electrolytes, and other such analytes used in
diagnostic medicine and analytical chemistry. As used herein,
techniques to use biomedical devices to analyze biomarkers may be
useful to monitor for changes in a patient's biome which may be
indicative of early or advanced stages of the acquisition of lung
cancer. The techniques may also probe for the presence of an
infectious agent particularly of the lungs which may increase the
chance of acquisition of lung cancer. As mentioned previously some,
of the non-specific sensor protocols and devices may be coated with
antibodies or other biological molecules that may allow for a
signal change in the sensing device when a pathogen comes in
contact with the device surface.
Fluorescence-Based Probe Elements for Analyte Analysis
[0096] Various types of analytes may be detected and analyzed using
fluorescence based analysis techniques. A subset of these
techniques may involve the direct fluorescence emission from the
analyte itself. A more generic set of techniques relate to
fluorescence probes that have constituents that bind to analyte
molecules and in doing so alter a fluorescence signature. For
example, in Forster Resonance Energy Transfer (FRET), probes are
configured with a combination of two fluorophores that may be
chemically attached to interacting proteins. The distance of the
fluorophores from each other may affect the efficiency of a
fluorescence signal emanating therefrom.
[0097] One of the fluorophores may absorb an excitation irradiation
signal and may resonantly transfer the excitation to electronic
states in the other fluorophore. The binding of analytes to the
attached interacting proteins may disturb the geometry and cause a
change in the fluorescent emission from the pair of fluorophores.
Binding sites may be genetically programmed into the interacting
proteins, and for example, a binding site, which is sensitive to
glucose, may be programmed. In some cases, the resulting site may
be less sensitive or non-sensitive to other constituents in
interstitial fluids of a desired sample.
[0098] The binding of an analyte to the FRET probes may yield a
fluorescence signal that is sensitive to glucose concentrations. In
some exemplary embodiments, the FRET-based probes may be sensitive
to as little as a 10 .mu.M concentration of glucose and may be
sensitive to up to hundreds of micromolar concentrations. Various
FRET probes may be genetically designed and formed. The resulting
probes may be configured into structures that may assist analysis
of interstitial fluids of a subject. Alternatively, a sensing
devices may present a membrane to air which allows for the
diffusion of analytes through the membrane and into a fluid layer
containing the FRET probes. An array of differently tuned FRET
probes may provide flexible but specific sensing capable for a
number of types of analytes ranging from biological molecules to
environmental molecules of interest.
[0099] In some exemplary embodiments, the probes may be placed
within a matrix of material that is permeable to either
interstitial fluids when located in a patient, or to the fluids of
the analytical device which surround the FRET probes. For example,
different FRET probes may be assembled into hydrogel structures. In
some exemplary embodiments, these hydrogel probes may be included
into the hydrogel based processing of ophthalmic contact lenses in
such a manner that they may reside in a hydrogel encapsulation that
is immersed in tear fluid when worn upon the eye. In other
exemplary embodiments, the probe may be inserted in the ocular
tissues just above the sclera. A hydrogel matrix comprising
fluorescence emitting analyte sensitive probes may be placed in
various locations that are in contact with bodily fluids containing
an analyte. Since the eye is exposed to the environment, it may be
possible for a contact lens that is worn to provide monitoring
capability for the environment of the patient. In other examples,
the hydrogel with imbedded FRET probes may reside in a sensor
device which contains the necessary fluorescence light sources and
detectors to read out signals from the FRET probes, which may be
assembled in an array format.
[0100] In an example of an ophthalmic sensor within the body of a
pre-disposed patient, the fluorescence probes may be in contact
with interstitial fluid of the ocular region near the sclera. In
these cases, where the probes are invasively embedded, a sensing
device may provide a radiation signal incident upon the
fluorescence probe from a location external to the eye such as from
an ophthalmic lens or a handheld device held in proximity to the
eye. FRET probes may be engineered to be sensitive to proteins and
hormones that may be indicative of the growth of lung cancer as has
been previously described.
[0101] In other exemplary embodiments, the probe may be embedded
within an ophthalmic lens in proximity to a fluorescence-sensing
device that is also embedded within the ophthalmic lens. In some
exemplary embodiments, a hydrogel skirt may encapsulate both an
ophthalmic insert with a fluorescence detector as well as a
FRET-based analyte probe. Further enablement for the use of
fluorescence detectors in biomedical devices may be found as set
forth in U.S. patent application Ser. No. 14/011,902 filed Aug. 28,
2013, which is incorporated herein by reference.
[0102] In some examples, a non-specific chemical detector may be
fashioned based on fluorescence based analysis. The analysis device
may be configured to interact with gaseous chemicals in the breath
of patients. When breathed upon, a sensor plate which may include
dozens of different sensor "spots" may interact with the various
gases in the patient's breath. The test apparatus may then have its
fluorescence spectrum characterized. Much like other
non-characteristic sensors, the probe may be "trained" to obtain
the unique spectral response for different analytes and then these
characteristic results may be assembled into a database that is
used in analyzing the overlap result.
[0103] In some examples, the absolute levels of analytes may form
only one basis for determining a concern. Alternatively, or in
addition to comparing measurements to a predetermined or absolute
threshold, a baseline for the healthy patient may be established
and the detectors may be utilized to detect changes from this
baseline. A change in measurements over time may signal the
approach of a condition that will inevitably exceed the threshold,
and detection of the time dependent change may afford earlier
detection effectiveness. It is also possible that a spectrum of
disease states and concomitant analyte generation may vary
depending on the exact state of disease. In such cases, it may not
be possible to determine a completely effective threshold action
value, thus the use of changes from a baseline value for a given
individual may be an effective method of detection and proactive
treatment.
[0104] Various types of non-specific sensors may be configured into
an array which may be used to sense ambient for chemical
composition. A clearly important type of ambient that may be sensed
from a health perspective may be the breath of a patient. The
breath of a patient may contain a large array of different chemical
constituents including in non-limiting examples 2-ethylhexanol,
3-methylhexane, 5-ethyl-3-methyloctane, acetone, ethanol,
ethylacetate, ethylbenzene, isononane, isoprene, nonanal, styrene,
toluene, and undecane. For various diseases the relative levels of
these chemicals may differ significantly. Detection of these
constitutents and an ability to monitor a portfolio of the
chemicals in a sample of a patients breath may be understanding of
disease states that may occur in patients. For example, studies
have shown that in the breath of patients with lung cancer that the
breath of these patients contains significant levels of some of
these chemicals. In examples the chemicals typically present may
include: 2-ethylhexanol; 3-methylhexane; ethanol; isononane;
isoprene; nonanal; styrene; and toluene. Other important analytes
may be present in lower levels that these examples.
[0105] It has been demonstrated that a cancer-related gas detector
may be assembled with a relatively small (about 50 millimeter
diameter) circular plate. On the plate are sensitive spots to form
a fluorescent cross-responsive sensor array. The sensor may consist
of a disposable array with dozens of chemically responsive spots
located around the sensor edge. The spots may then be filled with
different samples of sensitive synthetic compounds. Interaction of
such a fluorescence cross-responsive array with specific analytes
or volatile organic compound gases may cause the characteristic
shifts in fluorescence characteristics of the spots. By collecting
the fluorescent emission spectrum of the sensor array before and
after the reaction, a dataset may be obtained which may be analyzed
across a database of known analytes to determine the best fit set
of chemicals that can explain the shifts in the fluorescence
response of the dozens of test sites. Probes based on these
principles may be fashioned into various form factors which may
interact with the breath of a patient.
Sensing Devices with Event Coloration Mechanism
[0106] Another method of detecting analytes may be a passive
coloration scheme wherein analytes may strictly bind to a reactive
compound resulting in a color change which may indicate the
presence of a specific analyte. Such probes may be formulated into
stand-alone sensing elements which use spectroscopy to detect
changes in the coloration scheme. In other examples, the coloration
may be detected as a signal that a pre-disposed risk lung cancer
patient may visually see. In the following paragraphs description
of such a visual scheme in a contact lens where the optic zone of
the lens may change color at least in a part is described. It may
be noted that the use of the various coloration technology may
alternatively be disposed into portable sensors with or without
spectroscopic readout of various kinds that are not worn on the
eye.
[0107] In proceeding with an ophthalmic example, an event
coloration mechanism may comprise a reactive mixture, which, for
example, may be added to, printed on, or embedded in a rigid insert
of an ophthalmic device, such as through thermoforming techniques.
Alternatively, the event coloration mechanism may not require a
rigid insert but instead may be located on or within a hydrogel
portion, for example, through use of printing or injection
techniques.
[0108] The event coloration mechanism may comprise a portion of a
rigid insert that is reactive to some component of the transient
tear fluid or some component within an ophthalmic lens. For
example, the event may be a specific accumulation of some
precipitant, such as, lipids or proteins, on either or both the
rigid ophthalmic insert and a hydrogel portion, depending on the
composition of the ophthalmic 1 ens. The accumulation level may
"activate" the event coloration mechanism without requiring a power
source. The activation may be gradual wherein the color becomes
more visible as the accumulation level increases, which may
indicate when the ophthalmic 1 ens needs to be cleaned or
replaced.
[0109] Alternatively, the color may only be apparent at a specific
level. In some embodiments, the activation may be reversible, for
example, where the wearer effectively removes the precipitant from
the hydrogel portion or the rigid insert. The event coloration
mechanism may be located outside the optic zone, which may allow
for an annular embodiment of the rigid insert. In other
embodiments, particularly where the event may prompt a wearer to
take immediate action, the event coloration mechanism may be
located within the optic zone, allowing the wearer to see the
activation of the event coloration mechanism.
[0110] In some other embodiments, the event coloration mechanism,
may comprise a reservoir containing a colored substance, for
example, a dye. Prior to the occurrence of the event, the reservoir
may not be visible. The reservoir may be encapsulated with a
degradable material, which may be irreversibly degraded by some
constituent of the tear fluid, including, for example, proteins or
lipids. Once degraded, the colored substance may be released into
the ophthalmic lens or into a second reservoir. Such an embodiment
may indicate when a disposable ophthalmic lens should be disposed
of, for example, based on a manufacturer's recommended
parameters.
[0111] Proceeding to FIGS. 5A and 5B, an exemplary embodiment of an
ophthalmic lens 500 with multiple event coloration mechanisms
501-508 is illustrated. In some embodiments, the event coloration
mechanisms 501-508 may be located within the soft, hydrogel portion
510 of the ophthalmic lens 500 and outside the optic zone 509.
[0112] Such embodiments may not require a rigid insert or media
insert for functioning of the event coloration mechanisms 501-508,
though inserts may still be incorporated in the ophthalmic lens 500
allowing for additional functionalities. In some embodiments, each
event coloration mechanism 501-508 may be separately encapsulated
within the soft, hydrogel portion 510 of the ophthalmic lens 500.
The contents of the event coloration mechanisms 501-508 may include
a compound reactive to some condition, such as temperature, or
component of tear fluid, such as a biomarker.
[0113] In some embodiments, each event coloration mechanism 501-508
may "activate" based on different events. For example, one event
coloration mechanism 508 may comprise liquid crystal that may react
to changes in temperatures of the ocular environment, wherein the
event is a fever. Other event coloration mechanisms 502-506 within
the same ophthalmic lens 500 may react to specific pathogens, for
example, those that may cause ocular infections or may be
indicative of non-ocular infections or diseases, such as keratitis,
conjunctivitis, corneal ulcers, and cellulitis. Such pathogens may
include, for example, Mycobacterium tuberculosis, Acanthamoeba
keratitis, Pseudomona aeruginosa, Neisseria gonorrhoeae, and
Staphylococcus and Streptococcus strains, such as S. aureus. Some
of these pathogens may be risk factors for patients with elevated
or high pre-disposition to acquisition of lung cancer, others may
be opportunistic infections which may occur in the presence of a
lung cancer state before or after it is being treated.
[0114] The event coloration mechanisms 501-507 may be encapsulated
with a compound that may be selectively permeable to a component of
tear fluid. In some embodiments, the event coloration mechanisms
502-506 may function by agglutination, such as through a coagulase
test, wherein a higher concentration of the pathogen may adhere to
a compound within the event coloration mechanisms 502-506 and may
cause clumping or the formation of precipitate. The precipitate may
provide coloration or may react with another compound in the event
coloration mechanisms 502-506 through a separate reaction.
Alternatively, the event coloration mechanisms 502-506 may comprise
a reagent that colors upon reaction, such as with some oxidase
tests.
[0115] As shown in cross section 520 in FIG. 5B, the event
coloration mechanisms 522, 525 may be located in the periphery of
the ophthalmic lens without altering the optical surface of the
hydrogel portion 530. In some embodiments, not shown, the event
coloration mechanisms may be located at least partially within the
optic zone 529, alerting the wearer of the event. The locations of
the event coloration mechanisms 522, 525 may be varied within a
single ophthalmic lens 500, with some in the periphery and some
within the optic zone 529.
[0116] Referring to FIGS. 6A and 6B, an alternative exemplary
embodiment of an ophthalmic lens 600 with an optic zone 601 and a
non-optic zone 602 with event coloration mechanisms 611-614,
621-624, and 631-634 is illustrated. In some such embodiments, the
event mechanisms 611-614, 621-624, and 631-634 may include a
reactive molecule 612-614, 622-624, and 632-634 respectively,
anchored within the ophthalmic lens 600. The reactive molecule
612-614, 632-634 may comprise a central binding portion 613, 633
flanked by a quencher 612, 632 and a coloration portion 614, 634,
for example, a chromophore or fluorophore. Depending on the
molecular structure, when a specified compound binds to the binding
portion 613, 633, the coloration portion 614, 634 may shift closer
to the quencher 612, reducing coloration, or may shift away from
the quencher 632, which would increase coloration. In other
embodiments, the reactive molecule 622-624 may comprise a binding
portion 623 flanked by Forster resonance energy transfer pairs 622,
624. FRET pairs 622, 624 may function similarly to a quencher 612,
632 and chromophore (the coloration portion) 614, 634, though FRET
pairs 622, 624 may both exhibit coloration and, when in close
proximity to each other, their spectral overlap may cause a change
in coloration.
[0117] The reactive molecule 612-614, 622-624, and 632-634 may be
selected to target specific compounds within the tear fluid. In
some embodiments, the specific compound may directly indicate the
event. For example, where a level of glucose in the tear fluid is
the event, the reactive molecule 612-614, 622-624, and 632-634 may
directly bind with the glucose. Where the event is the presence or
concentration of a pathogen, for example, a particular aspect of
that pathogen may bind with the reactive molecule 612-614, 622-624,
and 632-634. This may include a unique lipid or protein component
of that pathogen. Alternatively, the specific compound may be an
indirect indicator of the event. The specific compound may be a
byproduct of the pathogen, such as a particular antibody that
responds to that pathogen.
[0118] As illustrated in cross section in FIG. 6B, the placement of
the reactive molecules 660, 680 within the ophthalmic lens 650 may
be varied within the hydrogel 652. For example, some reactive
molecules 680 may be entirely in the periphery with no overlap with
the optic zone 651. Other reactive molecules 660 may at least
partially extend into the optic zone 651. In some such embodiments,
the reactive molecules 660 may extend into the optic zone 651 in
some configurations of that reactive molecule 660, such as when the
event has occurred, which may alert the wearer of the event.
[0119] Further enablement for the use of event detectors in
biomedical devices may be found as set forth in U.S. patent
application Ser. No. 13/899,528 filed May 21, 2013, which is
incorporated herein by reference.
Quantum-Dot Spectroscopy
[0120] Small spectroscopy devices may be of significant aid in
creating biomedical devices with the capability of measuring and
controlling concentrations of various analytes for a user. Current
micro spectrometer designs mostly use interference filters and
interferometric optics to measure spectral responses of mixtures
that contain materials that absorb light. In some examples a
spectrometer may be formed by creating an array composed of
quantum-dots. A spectrometer based on quantum-dot arrays may
measure a light spectrum based on the wavelength multiplexing
principle. The wavelength multiplexing principle may be
accomplished when multiple spectral bands are encoded and detected
simultaneously with one filter element and one detector element,
respectively. The array format may allow the process to be
efficiently repeated many times using different filters with
different encoding so that sufficient information is obtained to
enable computational reconstruction of the target spectrum. An
example may be illustrated by considering an array of light
detectors such as that found in a charge-coupled device (CCD)
camera. The array of light sensitive devices may be useful to
quantify the amount of light reaching each particular detector
element in the CCD array. In a broadband spectrometer, a plurality,
sometimes hundreds, of quantum-dot based filter elements are
deployed such that each filter allows light to pass from certain
spectral regions to one or a few CCD elements. An array of hundreds
of such filters laid out such that an illumination light passed
through a sample may proceed through the array of Quantum Dot
(referred to as QD) Filters and on to a respective set of CCD
elements for the QD filters. The simultaneous collection of
spectrally encoded data may allow for a rapid analysis of a
sample.
[0121] Narrow band spectral analysis examples may be formed by
using a smaller number of
[0122] QD filters surrounding a narrow band. In FIG. 7A an
illustration of how a spectral band may be observed by a
combination of two filters is illustrated. It may also be clear
that the array of hundreds of filters may be envisioned as a
similar concept to that in FIG. 7A repeated many times.
[0123] In FIG. 7A, a first QD filter 780 may have an associated
spectral absorption response as illustrated and indicated as ABS on
the y-axis. A second QD filter 781 may have a shifted spectral
absorption associated with a different nature of the quantum-dots
included in the filter, for example, the QDs may have a larger
diameter in the QD filter 781. The difference curve of a flat
irradiance of light of all wavelengths (white light) may result
from the difference of the absorption result from light that
traverses filter 781 and that traverses filter 780. Thus, the
effect of irradiating through these two filters is that the
difference curve would indicate spectral response in the depicted
transmission band 782, where the y-axis is labelled Trans to
indicate the response curve relates to transmission
characteristics. When an analyte is introduced into the light path
of the spectrometer, where the analyte has an absorption band in
the UV/Visible spectrum, and possibly in the infrared, the result
would be to modify the transmission of light in that spectral band
as shown by spectrum 783. The difference from 782 to 783 results in
an absorption spectrum 784 for the analyte in the region defined by
the two quantum-dot filters. Therefore, a narrow spectral response
may be obtained by a small number of filters. In some examples,
redundant coverage by different filter types of the same spectral
region may be employed to improve the signal to noise
characteristics of the spectral result.
[0124] The absorption filters based on QDs may include QDs that
have quenching molecules on their surfaces. These molecules may
stop the QD from emitting light after it absorbs energy in
appropriate frequency ranges. More generally, the QD filters may be
formed from nanocrystals with radii smaller than the bulk
excitation Bohr radius, which leads to quantum confinement of
electronic charges. The size of the crystal is related to the
constrained energy states of the nanocrystal and generally
decreasing the crystal size has the effect of a stronger
confinement. This stronger confinement affects the electronic
states in the quantum-dot and results in an increase in the
effective bandgap, which results in shifting to the blue
wavelengths both of both optical absorption and fluorescent
emission. There have been many spectral limited sources defined for
a wide array of quantum-dots that may be available for purchase or
fabrication and may be incorporated into biomedical devices to act
as filters. By deploying slightly modified QDs such as by changing
the QD's size, shape and composition it may be possible to tune
absorption spectra continuously and finely over wavelengths ranging
from deep ultraviolet to mid-infrared. QDs may also be printed into
very fine patterns.
Biomedical Devices with Quantum-Dot Spectrometers
[0125] FIG. 7B illustrates an exemplary QD spectrometer system in a
biomedical device 700. The illustration in FIG. 7B may utilize a
passive approach to collecting samples wherein a sample fluid
passively enters a channel 702. The channel 702 may be internal to
the biomedical device 700 in some examples and in other examples,
as illustrated, the biomedical device 700 may surround an external
region with a reentrant cavity. In some examples where the
biomedical device 700 creates a channel of fluid external to
itself, the device 700 may also contain a pore 760 to emit reagents
or dyes to interact with the external fluid in the channel region.
Such biomedical devices may be included in various types of sensing
locations including in a non-limiting sense, dental appliances and
implants, eating implements and the like. Specific probing devices,
which may require an overt testing operation by the user, such as a
probe in the shape of a tongue depressor may also function by being
placed into the mouth of a patient who is predisposed to the
acquisition of lung cancer and may sense the spectral
characteristics of the patient's breath.
[0126] In a non-limiting sense, the passive sampling may be
understood with reference to an example where the biomedical device
700 may be a swallowable pill. The pill may comprise regions that
emit medicament 750 as well as regions that analyze surrounding
fluid such as gastric fluid for the presence of an analyte, where
the analyte may be the medicament, for example, but also may be
evidence of environmental agents that the patient has been exposed
to that have made their way down the esophagus and into the gastric
fluid. The pill may contain controller 770 regions. An analysis
region 703 may comprise a reentrant channel 702 within the
biomedical pill device that allows external fluid to passively flow
in and out of the channel. When an analyte, for example, in gastric
fluid, diffuses or flows into the channel 702 it becomes located
between the analysis regions 703 as depicted in FIG. 7B.
[0127] Referring now to FIG. 7C, once an analyte diffuses or
otherwise enters the quantum-dot spectrometer channel which shall
be referred to as the channel 702, a sample 730 may pass in the
emission portion of a quantum-dot (QD) emitter 710. The QD emitters
710 may receive information from a QD emitter controller 712
instructing the QD emitters 710 to emit an output spectrum of light
across the channel 702.
[0128] In some examples, the QD emitter 710 may act based on
emission properties of the quantum-dots. In other examples, the QD
emitter may act based on the absorption properties of the
quantum-dots. In the examples utilizing the emission properties of
the quantum-dots, these emissions may be photostimulated or
electrically stimulated. In some examples of photostimulation;
energetic light in the violet to ultraviolet may be emitted by a
light source and absorbed in the quantum-dots. The excitation in
the QD may relax by emitting photons of characteristic energies in
a narrow band. As mentioned previously, the QDs may be engineered
for the emission to occur at selected frequencies of interest.
[0129] In a similar set of examples, QDs may be formed into a set
of layers. The layers may place the QDs between electrically active
layers that may donate electrons and holes into the QDs. These
excitations, due to the donations of electrons and holes may
similarly stimulate the QDs to emit characteristic photons of
selected frequency. The QD emitter 710 may be formed by inclusion
of nanoscopic crystals, that function as the quantum-dots, where
the crystals may be controlled in their growth and material that
are used to form them before they are included upon the emitter
element.
[0130] In an alternative set of examples, where the QDs act in an
absorption mode a combination of a set of filters may be used to
determine a spectral response in a region. This mechanism is
described in a prior section in reference to FIG. 7A. Combinations
of QD absorption elements may be used in analysis to select regions
of the spectrum for analysis.
[0131] In either of these types of emission examples, a spectrum of
light frequencies may be emitted by QD emitter 710 and may pass
thru the sample 730. The sample 730 may absorb light from some of
the emitted frequencies if a chemical constituent within the sample
is capable of absorbing these frequencies. The remaining
frequencies that are not absorbed may continue on to the detector
element, where QD receivers 720 may absorb the photons and convert
them to electrical signals. These electrical signals may be
converted to digital information by a QD detector sensor 722. In
some examples the sensor 722 may be connected to each of the QD
receivers 720, or in other examples the electrical signals may be
routed to centralized electrical circuits for the sensing. The
digital data may be used in analyzing the sample 730 based on
pre-determined values for QD wavelength absorbance values.
[0132] In FIG. 7D, the QD system is depicted in a manner where the
sample is passed in front of spectral analysis elements that are
spatially located. FIGS. 7C and 7D depict such movement as the
difference between the locations of the sample 730 which has moved
from a first location 731 along the analysis region to the new
location 732. In other examples the QDs may be consolidated to act
in a single multidot location where the excitation means and the
sensing means are consolidated into single elements for each
function. Some biomedical devices may have space limitations for a
spectrometer comprising more than a hundred quantum-dot devices,
but other biomedical devices may have hundreds of quantum-dot
devices which allow for a full spectrographic characterization of
analyte containing mixtures.
[0133] The QD analytical system may also function with microfluidic
devices to react samples containing analytes with reagents
containing dyes. The dye molecules may react with specific
analytes. As mentioned previously, an example of such a binding may
be the FRET indicators. The dye molecules may have absorption bands
in the ultraviolet and visible spectrum that are significantly
strong, which may also be referred to as having high extinction
coefficients. Therefore, small amounts of a particular analyte may
be selectively bound to molecules that absorb significantly at a
spectral frequency, which may be focused on by the QD analytical
system. The enhanced signal of the dye complex may allow for more
precise quantification of analyte concentration.
[0134] Although described in concert with a swallowable pill it may
be obvious how a quantum dot spectroscopy device may represent a
small and flexible spectroscopy apparatus that may be incorporated
into various sensing devices as have been described in the
specification herein.
Exemplary Monitoring Paradigms
[0135] Referring now to FIGS. 8A-8E, a number of exemplary means of
deploying a monitoring apparatus are illustrated. Some of the
illustrated means have been discussed in previous sections, but are
brought here to illustrate the type of characteristics of personal
monitoring that may have relevance to the monitoring of a patient
who has an elevated or high propensity of acquiring lung cancer.
The lungs may be distinct because they have such a significant
surface area that is in contact with external air for an internal
organ. The risks of environmental exposures in general may relate
to the exposure of an agent in the environment to an individual
where the agent is inhaled into the lung tissue of the predisposed
patient. Thus, it may be advantageous to define sensing modalities
that interact in easy ways with the potential exposure of the
patient. It is important to understand that routine household
chores, for example cleaning, as well as more involved work around
the house, for example, carpentry and dry walling, may place an
individual with a genetic predisposition at risk. Household
cleaners, dust, drywall compound and sawdust are amongst the
materials that may potentially cause a problem.
[0136] For example, a first modality may be to associate a sensing
device with an electronic means that may have computational
abilities, may have communication capabilities and desirably may
interact with the air proximate to the mouth of a patient. A cell
phone 810 in FIG. 8A may provide an excellent example of such an
apparatus. In normal operation, a cell phone is frequently held to
a user's mouth as he or she speaks into the phone. Sensing
equipment may therefore sense the breath of the user. In some
examples, the sensing equipment may monitor the air in its vicinity
and therefore due to its frequent proximity to a user's mouth it
will frequently monitor the air in extremely relevant manners. The
cell phone 810 may include various sensing devices that may be part
of the phone, or may be connected to the phone as a case or an
attachment. The cell phone 810 also is an ideal means to deliver
various communication to a user. Through cellular, wireless,
Bluetooth or other communication means if enabled, the cell phone
can receive messages and communicate them via video screens,
vibrational transducers, and audio speakers as non-limiting
examples.
[0137] A second exemplary modality may be illustrated in FIG. 8B as
a dental appliance 820. The dental appliance may be a brace or
bridge that may be placed into the mouth or reside in the mouth. In
other examples, an oral appliance may include various sensing
devices that may sense the breath of a user, the saliva of a user,
or both. As has been discussed each may contain chemicals and
particles that are in the environment. In some examples, chemicals
and gasses may be released by the user's body which may indicate a
status related to lung cancer.
[0138] A third exemplary modality may be illustrated in FIG. 8C as
eating appliances 830. In some examples, implements that are used
for eating may include sensors to sense the breath of an individual
who is using them. In some examples, the saliva of the user may
also be sensed by the eating appliances 830 such as a fork, knife
and/or spoon.
[0139] A fourth exemplary modality for personal monitoring may be
illustrated in FIG. 8D as a wrist based sensor 840 such as a smart
watch or an electronic bracelet. The wrist based sensor 840 may
include a device that may monitor the air in its vicinity. The
wrist based sensor 840 may include various sensing devices that may
be part of a smart watch, or may be connected to the watch as a
case or an attachment. In some examples, the wrist based sensor 840
may be a bracelet that includes sensing devices. The wrist based
sensor 840 also may be an ideal means to deliver various
communication to a user. Through cellular, wireless, Bluetooth or
other communication means if enabled, the smart watch can receive
messages and communicate them via video screens, vibrational
transducers, and audio speakers as non-limiting examples.
[0140] A fifth exemplary modality for personal sensing may be
illustrated in FIG. 8E as a sensor-enabled sanitary device 850 such
as a toilet equipped with sensors. In excrement from a user there
may be numerous chemicals that may indicate a disease state such as
lung cancer. A sanitary device may be able to facilitate the
acquisition of samples that may be analyzed. In some examples, a
personal device of the user such as a smart phone or a smart watch
may communicate with the sensor enabled sanitary device 850 and
communicate information identifying the user with any sample
obtained. Other sanitary sensors may include sanitary napkins,
tampons and adult diapers.
[0141] There may be many other types of personal sensing modalities
that may allow for the sensing of either user proximate
environmental conditions or alternatively user biomedical status.
The examples discussed are not meant to limit the diversity of
different manners and methods under which sensing may occur. The
results of the sensing may provide important information for users
with pre-disposition to the acquisition of lung cancer.
Methods
[0142] There are numerous methods by which specialized sensor
technology may be deployed to assist patients with elevated or high
pre-disposition to the acquisition of lung cancer in following
practices which reduce the chance the individual has for acquiring
lung cancer by lowering his or her exposure to environmental
agents. Referring to FIG. 9, a first example of such methodology is
illustrated. At 910, a patient may have a sample of their genetic
material taken and submitted for analysis. Including the examples
set forth above as well as those identified in the future, there
may be numerous genetic locations where variations may be analyzed
and used to determine a genetic propensity of the patient to
develop lung cancer as shown in step 920. In some examples, it may
be determined at step 930 that the patient does not have an
elevated or high propensity to develop lung cancer as is depicted
at step 931. In other examples, the patient may have an elevated or
high propensity to develop lung cancer as illustrated at step 940.
For these patients, a prudent step illustrated at step 950 may
include monitoring of the environment of the patient with one or
more of personal monitoring devices, home monitoring devices and
work monitoring devices as the many examples discussed herein has
depicted. In some examples, as illustrated in the optional step
960, the patient who is predisposed may be equipped with a
geolocation device which may determine his or her location along
with accurate time and date stamps in a database. The location and
time data may be married with other databases such as databases of
"Smart Cities" where cities deploy a myriad of sensors in their
neighborhoods and pass that information into large city related
databases. Environmental sensing is an important type of data that
is being sensed in current operations. There may be numerous
agencies and organizations that sense the environment of specific
locations and then store the analysis results. Under free or
fee-based models the data may be accessed by applications that the
lung patient may have access to. Based on the systems sensors or on
the marriage of location and time state data with environmental
databases, a state of elevated exposure may be detected by
algorithms running in applications of the user. At step 970, the
patient may receive a warning that is communicated to him or her by
the algorithm. The warning may indicate to the user that an
environmental agent has been detected in an abundant level and may
suggest actions that the user may take. At step 980, the user may
take one or more of the actions to ameliorate the exposure to the
environmental agents. In some examples, the patient may exit the
area of the sensed elevated level of environmental agents. In some
other examples, the patient may use protective apparel to shield
him or herself from exposure, for example, a simple surgical mask.
At step 990, because the patient may have been exposed to an
elevated level of an environmental agent which may be suspected to
increase the potential of the patient to acquiring lung cancer, he
or she may be identified as a patient where increased medical
scanning and monitoring for deleterious effects of the historic
exposures of the patient to the environmental agents is performed
proactively. In addition to monitoring, the patient may be given
some form of treatment to treat, reverse the damage if possible, or
protect the patient from potential future harm. Even with
ameliorative treatment, the measurements of exposure may still
guide for an enhanced monitoring scheme for development of cancer
which may include medical imaging studies and genetic monitoring
for mutation events, as well as standard monitoring for chemical
species in the breath of the patient at frequent intervals.
[0143] In some examples, it may be possible to stratify the risk
potential of a patient with some level of genetic variation related
to the development of lung cancer into more levels than just high
when there is evidence of variation and low when there is not.
There may be some "grey" levels which may be indicated by the
presence of certain types of variation or based on the number of
sites which show variation as examples. There may be some different
methodology for patients with elevated but not high levels of risk
potential.
[0144] Referring to FIG. 10, an example of different methodology
related to patients at genetically elevated risk of developing lung
cancer where the risk is stratified into an intermediate risk
level. In the example of FIG. 10, when compared to that of FIG. 9,
the level of monitoring may be modified as a non-limiting example.
Whereas a high risk patient may have monitors associated with work,
home and personal space as well as geolocation based tracking and
risk interpolation, an elevated risk patient may only have his
workspace and home monitored as non-limiting examples.
[0145] Referring to FIG. 10, at 1010, a patient may have a sample
of their genetic material taken and submitted for analysis. Given
the rapidly developing and evolving understanding of the genetic
correlation with lung cancer risk, the monitoring/alert devices in
accordance with the present invention may comprise update
mechanisms such that any new screening criteria and/or processes
may be directly uploaded or otherwise made available to the
monitoring/alert devices of the present invention. In some
examples, portions of the hardware of monitoring/alert devices may
be updated in a similar manner as the software updates or in
addition to the software updates to bring the monitoring/alert
devices in line with newly developed understanding.
[0146] Including the examples set forth above as well as those
identified in the future, there may be numerous genetic locations
where variations may be analyzed and used to determine a genetic
propensity of the patient to develop lung cancer as shown in step
1020. In some examples, it may be determined at step 1030 that the
patient does not have even an elevated propensity to develop lung
cancer as is depicted at step 1031. In other examples, the patient
may have just an elevated propensity to develop lung cancer as
illustrated at step 1040. For these patients, a prudent step
illustrated at step 1050 may include monitoring of the environment
of the patient with one or more of home monitoring devices and work
monitoring devices as the many examples discussed herein has
described. It may be determined that the generalized sensing of the
external environment is sufficient with home and work monitoring
devices and therefore that correlation to environmental databases
is not necessary.
[0147] At step 1060, the patient may receive a warning that is
communicated to him or her by the algorithm. The warning may
indicate to the user that an environmental agent has been detected
in an abundant level and may suggest actions that the user may
take. At step 1070, the user may take one or more of the actions to
ameliorate the exposure to the environmental agents. In some
examples, the patient may exit the area of the sensed elevated
level of environmental agents. In some other examples, the patient
may use protective apparel to shield him or herself from exposure.
At step 1080, because the patient may have been exposed to an
elevated level of an environmental agent which may be suspected to
increase the potential of the patient to acquiring lung cancer, he
or she may be identified as a patient where increased medical
scanning and monitoring for deleterious effects of the historic
exposures of the patient to the environmental agents is performed
proactively.
[0148] There may also be methods with use genetic assessment to
drive monitoring of an individual for the presence of biomarkers
that may indicate early stages or general occurrence of lung
cancer. Referring to FIG. 11, an example of methodology related to
detecting genetic propensity and then routinely monitoring high or
elevated risk patients for the presence of analytes indicating
advancement of disease. Referring to FIG. 11, at 1110, a patient
may have a sample of their genetic material taken and submitted for
analysis. Including the examples set forth above as well as those
identified in the future, there may be numerous genetic locations
where variations may be analyzed and used to determine a genetic
propensity of the patient to develop lung cancer as shown in step
1120. In some examples, it may be determined at step 1130 that the
patient does not have a high or elevated propensity to develop lung
cancer as is depicted at step 1131. In other examples, the patient
may have a high or elevated propensity to develop lung cancer as
illustrated at step 1140. For these patients, a prudent step
illustrated at step 1150 may include monitoring one or more of the
breath, saliva and lung tissue of the patient with one or more
types of monitoring devices for the analysis of the presence of
biomarkers of lung cancer.
[0149] At step 1160, in some cases sensors may detect potential
elevated levels of biomarkers and the patient may receive a warning
that is communicated to him or her by a monitoring systems which
interfaces the various sensors. The warning may indicate to the
user that biomarker may have been detected in an elevated level and
may suggest actions that the user may take. At step 1170, because
the patient may have indication via certain biomarkers that may
indicate that the high or elevated propensity patient's tissues are
undergoing changes consistent with lung cancer, he or she may be
identified as a patient where increased medical scanning and
monitoring for deleterious effects of the historic exposures of the
patient to the environmental agents is performed proactively.
[0150] Although shown and described is what is believed to be the
most practical and preferred embodiments, it is apparent that
departures from specific designs and methods described and shown
will suggest themselves to those skilled in the art and may be used
without departing from the spirit and scope of the invention. The
present invention is not restricted to the particular constructions
described and illustrated, but should be constructed to cohere with
all modifications that may fall within the scope of the appended
claims.
* * * * *